Scholars@Duke
Robert Frank Spurney

Robert Frank Spurney

Professor of Medicine
Medicine, Nephrology
spurn002@mc.duke.edu
Duke Box 103015, Durham, NC 27710
Box 103015, Duke University Medical Center, Durham, NC 27710

Selected Publications

Pharmacologic blockade of the natriuretic peptide clearance receptor promotes weight loss and enhances insulin sensitivity in type 2 diabetes.

Journal Article Transl Res · May 2023 While natriuretic peptides (NPs) are primarily known for their renal and cardiovascular actions, NPs stimulate lipolysis in adipocytes and induce a thermogenic program in white adipose tissue (WAT) that resembles brown fat. The biologic effects of NPs are ... Full text Link to item Cite

Blockade of the natriuretic peptide clearance receptor attenuates proteinuria in a mouse model of focal segmental glomerulosclerosis.

Journal Article Physiol Rep · November 2021 Glomerular podocytes play a key role in proteinuric diseases. Accumulating evidence suggests that cGMP signaling has podocyte protective effects. The major source of cGMP generation in podocytes is natriuretic peptides. The natriuretic peptide clearance re ... Full text Link to item Cite

Twist1 in podocytes ameliorates podocyte injury and proteinuria by limiting CCL2-dependent macrophage infiltration.

Journal Article JCI Insight · August 9, 2021 The transcription factor Twist1 regulates several processes that could impact kidney disease progression, including epithelial cell differentiation and inflammatory cytokine induction. Podocytes are specialized epithelia that exhibit features of immune cel ... Full text Link to item Cite

A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (RCAN1) Gene Confers Enhanced Calcineurin Activity and May Cause FSGS.

Journal Article J Am Soc Nephrol · July 2021 BACKGROUND: Podocyte dysfunction is the main pathologic mechanism driving the development of FSGS and other morphologic types of steroid-resistant nephrotic syndrome (SRNS). Despite significant progress, the genetic causes of most cases of SRNS have yet to ... Full text Link to item Cite

TRPC Channels in Proteinuric Kidney Diseases.

Journal Article Cells · December 23, 2019 Over a decade ago, mutations in the gene encoding TRPC6 (transient receptor potential cation channel, subfamily C, member 6) were linked to development of familial forms of nephrosis. Since this discovery, TRPC6 has been implicated in the pathophysiology o ... Full text Link to item Cite

Knockout of TRPC6 promotes insulin resistance and exacerbates glomerular injury in Akita mice.

Journal Article Kidney Int · February 2019 Gain-of-function mutations in TRPC6 cause familial focal segmental glomerulosclerosis, and TRPC6 is upregulated in glomerular diseases including diabetic kidney disease. We studied the effect of systemic TRPC6 knockout in the Akita model of type 1 diabetes ... Full text Link to item Cite

Regulation of cofilin phosphorylation in glomerular podocytes by testis specific kinase 1 (TESK1).

Journal Article Sci Rep · August 16, 2018 Expression of a constitutively active Rho A (V14Rho) in podocytes in vivo induces albuminuria and foot process (FP) effacement. These effects may be mediated by the Rho A effector Rho kinase (ROK); but inhibition of ROK with Y27632 failed to attenuate albu ... Full text Link to item Cite

The Human FSGS-Causing ANLN R431C Mutation Induces Dysregulated PI3K/AKT/mTOR/Rac1 Signaling in Podocytes.

Journal Article J Am Soc Nephrol · August 2018 BACKGROUND: We previously reported that mutations in the anillin (ANLN) gene cause familial forms of FSGS. ANLN is an F-actin binding protein that modulates podocyte cell motility and interacts with the phosphoinositide 3-kinase (PI3K) pathway through the ... Full text Link to item Cite

Podocyte-specific knockout of cyclooxygenase 2 exacerbates diabetic kidney disease.

Journal Article Am J Physiol Renal Physiol · August 1, 2017 Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to glomerular injury in diabetic kidney disease, but some basal level of podocyte COX2 expression might be required to promote podocyte attachment and/or survival. To investigate the r ... Full text Link to item Cite

Losing their footing: Rac1 signaling causes podocyte detachment and FSGS.

Journal Article Kidney Int · August 2017 Selective modulation of Rho GTPase activity in podocytes recapitulates characteristic features of human nephrosis. Using a mouse model, Robins et al. found that high levels of Rac1 activation in podocytes caused podocyte detachment and glomerulosclerosis. ... Full text Link to item Cite

Twenty years after ACEIs and ARBs: emerging treatment strategies for diabetic nephropathy.

Journal Article Am J Physiol Renal Physiol · November 15, 2015 Diabetic nephropathy (DN) is a serious complication of both type 1 and type 2 diabetes mellitus. The disease is now the most common cause of end-stage kidney disease (ESKD) in developed countries, and both the incidence and prevalence of diabetes mellitus ... Full text Link to item Cite

Gq signaling causes glomerular injury by activating TRPC6.

Journal Article J Clin Invest · May 2015 Familial forms of focal segmental glomerulosclerosis (FSGS) have been linked to gain-of-function mutations in the gene encoding the transient receptor potential channel C6 (TRPC6). GPCRs coupled to Gq signaling activate TRPC6, suggesting that Gq-dependent ... Full text Link to item Cite

A novel missense mutation of Wilms' Tumor 1 causes autosomal dominant FSGS.

Journal Article J Am Soc Nephrol · April 2015 FSGS is a clinical disorder characterized by focal scarring of the glomerular capillary tuft, podocyte injury, and nephrotic syndrome. Although idiopathic forms of FSGS predominate, recent insights into the molecular and genetic causes of FSGS have enhance ... Full text Link to item Cite

Mutations in the gene that encodes the F-actin binding protein anillin cause FSGS.

Journal Article J Am Soc Nephrol · September 2014 FSGS is characterized by segmental scarring of the glomerulus and is a leading cause of kidney failure. Identification of genes causing FSGS has improved our understanding of disease mechanisms and points to defects in the glomerular epithelial cell, the p ... Full text Link to item Cite

Phosphodiesterase 5 inhibition ameliorates angiontensin II-induced podocyte dysmotility via the protein kinase G-mediated downregulation of TRPC6 activity.

Journal Article Am J Physiol Renal Physiol · June 15, 2014 The emerging role of the transient receptor potential cation channel isotype 6 (TRPC6) as a central contributor to various pathological processes affecting podocytes has generated interest in the development of therapeutics to modulate its function. Recent ... Full text Link to item Cite

Special deLIVERy: podocyte injury promotes renal angiotensin II generation from liver-derived angiotensinogen.

Journal Article Kidney Int · May 2014 The role of the circulating renin-angiotensin system (RAS) in regulating systemic blood pressure and sodium balance is well established. More recently, researchers have turned their focus to the local generation of angiotensin II (Ang II) in specific tissu ... Full text Link to item Cite

Augmenting podocyte injury promotes advanced diabetic kidney disease in Akita mice.

Journal Article Biochem Biophys Res Commun · February 21, 2014 To determine if augmenting podocyte injury promotes the development of advanced diabetic nephropathy (DN), we created mice that expressed the enzyme cytosine deaminase (CD) specifically in podocytes of diabetic Akita mice (Akita-CD mice). In these mice, tr ... Full text Link to item Cite

The cytoskeletal regulatory scaffold protein GIT2 modulates mesenchymal stem cell differentiation and osteoblastogenesis.

Journal Article Biochem Biophys Res Commun · August 24, 2012 G protein-coupled receptor kinase interacting protein 2 (GIT2) is a signaling scaffold protein involved in the regulation of cytoskeletal structure, membrane trafficking, and G protein-coupled receptor internalization. Since dynamic cytoskeletal reorganiza ... Full text Link to item Cite

A novel role for type 1 angiotensin receptors on T lymphocytes to limit target organ damage in hypertension.

Journal Article Circ Res · June 8, 2012 Featured Publication RATIONALE: Human clinical trials using type 1 angiotensin (AT(1)) receptor antagonists indicate that angiotensin II is a critical mediator of cardiovascular and renal disease. However, recent studies have suggested that individual tissue pools of AT(1) rec ... Full text Link to item Cite

Mechanisms of the proteinuria induced by Rho GTPases.

Journal Article Kidney Int · June 2012 Featured Publication Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created ... Full text Link to item Cite

Diabetic kidney disease in FVB/NJ Akita mice: temporal pattern of kidney injury and urinary nephrin excretion.

Journal Article PLoS One · 2012 Featured Publication Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diab ... Full text Link to item Cite

A novel mouse model of podocyte depletion.

Journal Article Nephron Exp Nephrol · 2012 AIM: The goal of this study was to examine the capacity for glomerular repair after a podocyte-depleting injury. METHODS: We created transgenic (TG) mice expressing the yeast enzyme cytosine deaminase specifically in glomerular podocytes. In these TG anima ... Full text Link to item Cite

Calcineurin (CN) activation promotes apoptosis of glomerular podocytes both in vitro and in vivo.

Journal Article Mol Endocrinol · August 2011 Featured Publication To determine the role of Gq signaling and calcineurin (CN) activation in promoting apoptosis of glomerular podocytes, constitutively active Gq [Gq(+)] or CN [CN(+)] proteins were introduced into cultured podocytes using protein transduction by tagging the ... Full text Link to item Cite

Regulator of G protein signaling 5 is highly expressed in parathyroid tumors and inhibits signaling by the calcium-sensing receptor.

Journal Article Mol Endocrinol · May 2011 The molecular mechanisms responsible for aberrant calcium signaling in parathyroid disease are poorly understood. The loss of appropriate calcium-responsive modulation of PTH secretion observed in parathyroid disease is commonly attributed to decreased exp ... Full text Link to item Cite

A beta-arrestin-biased agonist of the parathyroid hormone receptor (PTH1R) promotes bone formation independent of G protein activation.

Journal Article Sci Transl Med · October 7, 2009 About 40% of the therapeutic agents in use today exert their effects through seven-transmembrane receptors (7TMRs). When activated by ligands, these receptors trigger two pathways that independently transduce signals to the cell: one through heterotrimeric ... Full text Link to item Cite

Inhibition of WNT signaling by G protein-coupled receptor (GPCR) kinase 2 (GRK2).

Journal Article Mol Endocrinol · September 2009 Featured Publication Activation of Wnt signaling pathways causes release and stabilization of the transcription regulator beta-catenin from a destruction complex composed of axin and the adenomatous polyposis coli (APC) protein (canonical signaling pathway). Assembly of this c ... Full text Link to item Cite

Gq-dependent signaling upregulates COX2 in glomerular podocytes.

Journal Article J Am Soc Nephrol · November 2008 Featured Publication Accumulating evidence suggests that upregulation of cyclooxygenase 2 (COX2) in glomerular podocytes promotes podocyte injury. Because Gq signaling activates calcineurin and calcineurin-dependent mechanisms are known to mediate COX2 expression, this study i ... Full text Link to item Cite

Stressed-out podocytes in diabetes?

Journal Article J Am Soc Nephrol · November 2008 Full text Link to item Cite

Beneficial effects of the Rho kinase inhibitor Y27632 in murine puromycin aminonucleoside nephrosis.

Journal Article Kidney Blood Press Res · 2008 Featured Publication BACKGROUND AND AIMS: Rho kinase (ROCK) inhibition reduces systemic blood pressure (BP) and decreases renal damage in animal models of kidney disease. The aim of this study was to determine if ROCK inhibition might have beneficial effects in glomerular dise ... Full text Link to item Cite

Galphaq-dependent signaling cascades stimulate water-seeking behavior.

Journal Article Am J Physiol Renal Physiol · October 2006 Featured Publication We used the mouse nephrin promoter to express a constitutively active Galphaq [Galphaq(Q>L)] transgene in mice. As previously reported, the transgene was expressed in kidney, pancreas, and brain, and the kidney phenotype was characterized by albuminuria an ... Full text Link to item Cite

G protein-coupled receptor (GPCR) kinase 2 (GRK2) inhibits canonical Wnt signaling.

Conference JOURNAL OF BONE AND MINERAL RESEARCH · September 1, 2006 Link to item Cite

Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation.

Journal Article J Biol Chem · April 21, 2006 Featured Publication Parathyroid hormone (PTH) regulates calcium homeostasis via the type I PTH/PTH-related peptide (PTH/PTHrP) receptor (PTH1R). The purpose of the present study was to identify the contributions of distinct signaling mechanisms to PTH-stimulated activation of ... Full text Link to item Cite

Transactivation of the epidermal growth factor receptor by angiotensin II in glomerular podocytes.

Journal Article Nephron Exp Nephrol · 2006 Featured Publication BACKGROUND/AIMS: Activation of angiotensin II (ANG2) receptors stimulates extracellular signal-regulated kinases (ERKs) that, in some cell systems, are mediated by transactivating the epidermal growth factor (EGF) receptor (EGFR) through mechanisms involvi ... Full text Link to item Cite

Lambda light chain deposition disease in a renal allograft.

Journal Article Transplant Proc · December 2005 Light chain deposition disease (LCDD) of the kidney is characterized by deposition of monoclonal light chains predominantly in glomeruli and in tubular basement membranes. The disease is frequently associated with a lymphoproliferative disorder, and the ma ... Full text Link to item Cite

Activation of Galpha q-coupled signaling pathways in glomerular podocytes promotes renal injury.

Journal Article J Am Soc Nephrol · December 2005 Featured Publication The glomerular podocyte plays a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by activation of cell surface G protein-coupled receptors (GPCR). Studies suggest that podocytes express GPCR that ar ... Full text Link to item Cite

Enhanced bone mass in mice lacking G protein-coupled receptor kinases.

Conference JOURNAL OF BONE AND MINERAL RESEARCH · September 1, 2005 Link to item Cite

Role of thromboxane A2 in the induction of apoptosis of immature thymocytes by lipopolysaccharide.

Journal Article Clin Diagn Lab Immunol · August 2005 Lipopolysaccharide (LPS) causes apoptotic deletion of CD4(+) CD8(+) thymocytes, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. Given the abundance of thromboxane-prostanoid (TP) receptors in CD4(+) CD8(+) thymocyte ... Full text Link to item Cite

Targeted overexpression of G protein-coupled receptor kinase-2 in osteoblasts promotes bone loss.

Journal Article Am J Physiol Endocrinol Metab · April 2005 Featured Publication To investigate the role of G protein-coupled receptor kinases (GRKs) in regulating bone formation in vivo, we overexpressed the potent G protein-coupled receptor (GPCR) regulator GRK2 in osteoblasts, using the osteocalcin gene-2 promoter to target expressi ... Full text Link to item Cite

Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system.

Journal Article J Clin Invest · April 2005 Featured Publication Angiotensin II, acting through type 1 angiotensin (AT(1)) receptors, has potent effects that alter renal excretory mechanisms. Control of sodium excretion by the kidney has been suggested to be the critical mechanism for blood pressure regulation by the re ... Full text Link to item Cite

Beta-arrestin- and G protein receptor kinase-mediated calcium-sensing receptor desensitization.

Journal Article Mol Endocrinol · April 2005 Featured Publication Extracellular calcium rapidly controls PTH secretion through binding to the G protein-coupled calcium-sensing receptor (CASR) expressed in parathyroid glands. Very little is known about the regulatory proteins involved in desensitization of CASR. G protein ... Full text Link to item Cite

Unmasking the osteoinductive effects of a G-protein-coupled receptor (GPCR) kinase (GRK) inhibitor by treatment with PTH(1-34).

Journal Article J Bone Miner Res · October 2004 Featured Publication UNLABELLED: The effects of GPCR systems in bone are regulated by a family of enzymes termed GRKs. We found that (1) GRK inhibition in osteoblasts has age-dependent effects on bone mass, and (2) the anabolic actions of GRK inhibition are revealed by treatme ... Full text Link to item Cite

Proinflammatory actions of thromboxane receptors to enhance cellular immune responses.

Journal Article J Immunol · December 15, 2003 Metabolism of arachidonic acid by the cyclo-oxygenase (COX) pathway generates a family of prostanoid mediators. Nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting COX, thereby reducing prostanoid synthesis. The efficacy of these agents in redu ... Full text Link to item Cite

Characterization of angiotensin II-receptor subtypes in podocytes.

Journal Article J Lab Clin Med · November 2003 Featured Publication Glomerular podocytes play a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by angiotensin II (Ang II) through activation of cell-surface receptors. Although studies suggest that podocytes express ... Full text Link to item Cite

Hypertension in Cyp2j5 null mice is estrogen responsive.

Conference JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY · November 1, 2003 Link to item Cite

Mice transgenic for FSGS-linked mutant actinin-4 (ACTN4) express elevated renal EGR-1 mRNA.

Conference JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY · November 1, 2003 Link to item Cite

Physiological impact of increased expression of the AT1 angiotensin receptor.

Journal Article Hypertension · October 2003 Featured Publication To test the effect of increased AT1 receptor expression on blood pressure, we used gene targeting to generate mouse lines with a tandem duplication of the AT1A receptor gene locus (Agtr1a) along with >10 kb of 5' flanking DNA. By successive breeding, we ge ... Full text Link to item Cite

Regulated expression of G protein-coupled receptor kinases (GRK's) and beta-arrestins in osteoblasts.

Journal Article Calcif Tissue Int · August 2003 Desensitization of G-protein coupled receptors (GPCR's) is largely mediated by a family of enzymes and protein co-factors termed GRKs and arrestins, respectively. In the present studies, we investigated expression of GRKs and arrestins in osteoblastic cell ... Full text Link to item Cite

Rho kinase promotes alloimmune responses by regulating the proliferation and structure of T cells.

Journal Article J Immunol · July 1, 2003 Coordinated rearrangements of the actin-myosin cytoskeleton facilitate early and late events in T cell activation and signal transduction. As many important features of cell shape rearrangement involve small GTP-binding proteins, we examined the contributi ... Full text Link to item Cite

Calcium-sensing receptor activation of rho involves filamin and rho-guanine nucleotide exchange factor.

Journal Article Endocrinology · October 2002 We investigated the role of Galphaq, filamin, Rho, the RhoGEF Lbc, and the C terminus of calcium-sensing receptor (CasR) in CasR signaling. We found that Ca(2+), Mg(2+), or the calcimimetic R isomer of N-(3-[2-chlorophenyl]propyl)-(R)-alpha-methyl-3-methox ... Full text Link to item Cite

Desensitization of the mouse thromboxane A2 receptor (TP) by G protein-coupled receptor kinases (Grks).

Journal Article Prostaglandins Other Lipid Mediat · September 2002 Featured Publication GRKs play a key role in regulating G protein-coupled receptor (GPCR) responsiveness. To investigate the role of GRKs in desensitization of TP, we replaced threonines with favorable phosphorylation motifs for GRKs (positions 226 and 230) with alanine. Mutan ... Full text Link to item Cite

Anabolic effects of a G protein-coupled receptor kinase inhibitor expressed in osteoblasts.

Journal Article J Clin Invest · May 2002 Featured Publication G protein-coupled receptors (GPCRs) play a key role in regulating bone remodeling. Whether GPCRs exert anabolic or catabolic osseous effects may be determined by the rate of receptor desensitization in osteoblasts. Receptor desensitization is largely media ... Full text Link to item Cite

Domains of the parathyroid hormone (PTH) receptor required for regulation by G protein-coupled receptor kinases (GRKs).

Journal Article Biochem Pharmacol · October 15, 2001 To investigate the domains of the parathyroid hormone (PTH) receptor required for regulation by G protein-coupled receptor kinases (GRKs), we created mutant PTH receptors lacking potential GRK-phosphorylation sites. Mutant #1 was truncated at amino acid 54 ... Full text Link to item Cite

Analysis of recombinant Phex: an endopeptidase in search of a substrate.

Journal Article Am J Physiol Endocrinol Metab · October 2001 X-linked hypophosphatemia (XLH) is caused by inactivating mutations of Phex, a phosphate-regulating endopeptidase. Further advances in our knowledge of the pathogenesis of XLH require identification of the biological function of Phex and its physiologicall ... Full text Link to item Cite

Regulation of thromboxane receptor (TP) phosphorylation by protein phosphatase 1 (PP1) and PP2A.

Journal Article J Pharmacol Exp Ther · February 2001 To investigate the protein phosphatases that dephosphorylate TP, human embryonic kidney cells (HEK293 cells) stably transfected with 12CA5-tagged TP were treated with TP agonist, washed, and then allowed to recover in the presence or absence of the cell-pe ... Link to item Cite

A role for leukotrienes in cyclosporine nephrotoxicity.

Journal Article Kidney Int · June 2000 BACKGROUND: Nephrotoxicity associated with cyclosporine A (CsA) administration is characterized by marked renal vasoconstriction, interstitial fibrosis, and arteriolar hypertrophy. While the molecular mechanisms of CsA toxicity are not well characterized, ... Full text Link to item Cite

Sensing of extracellular cations in CasR-deficient osteoblasts. Evidence for a novel cation-sensing mechanism.

Journal Article J Biol Chem · February 4, 2000 We isolated osteoblastic cell lines from wild-type (CasR(+/+)) and receptor null (CasR(-/-)) mice to investigate whether CasR is present in osteoblasts and accounts for their responses to extracellular cations. Osteoblasts from both CasR(+/+) and CasR(-/-) ... Full text Link to item Cite

G protein-coupled receptor kinase 6A phosphorylates the Na(+)/H(+) exchanger regulatory factor via a PDZ domain-mediated interaction.

Journal Article J Biol Chem · August 20, 1999 Featured Publication The Na(+)/H(+) exchanger regulatory factor (NHERF) is constitutively phosphorylated in cells, but the site(s) of this phosphorylation and the kinase(s) responsible for it have not been identified. We show here that the primary site of constitutive NHERF ph ... Full text Link to item Cite

Deficiency of 5-lipoxygenase abolishes sex-related survival differences in MRL-lpr/lpr mice.

Journal Article J Immunol · July 1, 1999 Leukotrienes, the 5-lipoxygenase (5LO) products of arachidonic acid metabolism, have many proinflammatory actions that have been implicated in the pathogenesis of a variety of inflammatory diseases. To investigate the role of LTs in autoimmune disease, we ... Link to item Cite

Aluminum is a weak agonist for the calcium-sensing receptor.

Journal Article Kidney Int · May 1999 BACKGROUND: Aluminum (Al3+) has diverse biological effects mediated through activation of a putative extracellular cation-sensing receptor. A recently identified calcium-sensing receptor (CaSR), which has been identified in target tissues for Al3+, may tra ... Full text Link to item Cite

Role of C-terminal serines in desensitization and phosphorylation of the mouse thromboxane receptor.

Journal Article J Biol Chem · October 23, 1998 To investigate the role of C-terminal hydroxyamino acids in desensitization of the receptor for thromboxane A2 (TxA2), we created a mutant TxA2 receptor (TP receptor) in which serines at positions 321, 322, and 328 were replaced with either alanine or glyc ... Full text Link to item Cite

Thromboxane A2modulates the fibrinolytic system in glomerular mesangial cells.

Journal Article Am J Physiol Renal Physiol · August 1, 1998 We examined the effects of thromboxane A2(TxA2) on the activities of the plasminogen-plasmin system in glomerular mesangial cells. When mesangial cells are exposed to the TxA2agonist U-46619, a substantial increase in production of plasminogen activator in ... Full text Link to item Cite

Structure-function of recombinant Na/H exchanger regulatory factor (NHE-RF).

Journal Article J Clin Invest · May 15, 1998 Inhibition of the renal brush border membrane (BBM) Na/H exchanger by cAMP-dependent protein kinase, PKA, requires participation of a recently cloned regulatory cofactor, Na/H exchanger-regulatory factor (NHE-RF). As deduced from the cDNA of this 358-amino ... Full text Link to item Cite

Effect of receptor number on desensitization of the mouse thromboxane receptor.

Journal Article Biochem Pharmacol · April 15, 1998 Desensitization of G-protein coupled receptors limits the physiologic effects of an agonist. Short-term desensitization mechanisms are critically dependent on receptor phosphorylation by protein kinases. The effectiveness of these regulatory mechanisms mig ... Full text Link to item Cite

The C-terminus of the thromboxane receptor contributes to coupling and desensitization in a mouse mesangial cell line.

Journal Article J Pharmacol Exp Ther · October 1997 To investigate regulatory domains of the thromboxane A2 (TxA2) receptor, we constructed a truncated form of the mouse TxA2 receptor and expressed it in a mesangial cell line. The mutant receptor lacked 22 amino acids in the C-terminus including four potent ... Link to item Cite

Thromboxane (TX) stimulates plasminogen activator inhibitor-1 (PAI-1) production by mesangial cells.

Conference JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY · September 1, 1996 Link to item Cite

Differential regulation of receptor-stimulated cyclic adenosine monophosphate production by polyvalent cations in MC3T3-E1 osteoblasts.

Journal Article J Bone Miner Res · June 1996 Extracellular cations have paradoxical trophic and toxic effects on osteoblast function. In an effort to explain these divergent actions, we investigated in MC3T3-E1 osteoblasts if polyvalent cations differentially modulate the agonist-stimulated cyclic ad ... Full text Link to item Cite

The Prostaglandin E(1) (PGE(1)) Analog Misoprostol Ameliorates Autoimmune Disease and Depletes T Lymphocytes in MRL-lpr/lpr Mice.

Journal Article Am J Ther · December 1995 MRL-lpr/lpr mice spontaneously develop an autoimmune disease similar to human systemic lupus erythematosus (SLE). Disease manifestations include anti-DNA autoantibody production, arthritis, vasculitis, and an immune-complex glomerulonephritis. The developm ... Full text Link to item Cite

Role of platelet activating factor in kidney transplant rejection in the rat.

Journal Article Kidney Int · August 1995 Platelet activating factor (PAF) is a potent lipid mediator with a broad range of biologic activities. Experimental evidence suggests that PAF plays a role in the pathogenesis of a variety of inflammatory processes including allograft rejection. In this st ... Full text Link to item Cite

5-Hydroxytryptamine2A receptors expressed in rat renal mesangial cells inhibit cyclic AMP accumulation.

Journal Article Mol Pharmacol · August 1995 Second messenger coupling of the 5-hydroxytryptamine (5-HT)2A receptor endogenous to cultured rat glomerular mesangial cells was studied. 5-HT induced an increase in total inositol phosphate levels (EC50 = 265 +/- 55 nM, maximum stimulation = 150 +/- 23%). ... Link to item Cite

FUNCTIONAL-CHARACTERIZATION OF A CATION SENSING MECHANISM IN OSTEOBLASTS

Conference JOURNAL OF BONE AND MINERAL RESEARCH · August 1, 1995 Link to item Cite

The effects of short-term treatment with the prostaglandin E1 (PGE1) analog misoprostol on inflammatory mediator production in murine lupus nephritis.

Journal Article Clin Immunol Immunopathol · May 1995 MRL-lpr/lpr mice spontaneously develop an autoimmune disease with nephritis similar to human systemic lupus erythematosus. In these animals, treatment with E-series prostaglandins ameliorates renal disease and prolongs survival, perhaps by modulating produ ... Full text Link to item Cite

Identification of a rat glomerular mesangial cell mitogenic 5-HT2A receptor

Journal Article American Journal of Physiology - Renal Fluid and Electrolyte Physiology · January 1, 1995 Previous studies have demonstrated the presence of mitogenic serotonin [i.e., 5-hydroxytryptamine (5-HT)] receptors on glomerular mesangial cells and have linked those receptors to a complicated array of intracellular and autocrine/ paracrine signaling pat ... Cite

Identification of a rat glomerular mesangial cell mitogenic 5-HT2A receptor.

Journal Article Am J Physiol · January 1995 Previous studies have demonstrated the presence of mitogenic serotonin [i.e., 5-hydroxytryptamine (5-HT)] receptors on glomerular mesangial cells and have linked those receptors to a complicated array of intracellular and autocrine/paracrine signaling path ... Full text Link to item Cite

Fish oil feeding modulates leukotriene production in murine lupus nephritis.

Journal Article Prostaglandins · November 1994 Diets enriched with fish oil (FO) ameliorate kidney disease in the MRL-lpr/lpr murine model of lupus nephritis. Although the mechanisms of this effect are not known, FO is rich in the polyunsaturated fatty acid eicosapentaenoic acid (EPA) which may have pr ... Full text Link to item Cite

Modulation of thromboxane receptor activation in rat glomerular mesangial cells.

Journal Article Am J Physiol · September 1994 Rat glomerular mesangial cells were used to investigate mechanisms of thromboxane A2 (TxA2) receptor regulation in the kidney. Exposure of mesangial cells to the TxA2 agonist U-46619 for 10 min reduced subsequent TxA2-induced increases in inositol phosphat ... Full text Link to item Cite

MODULATION OF THROMBOXANE RECEPTOR ACTIVATION IN RAT GLOMERULAR MESANGIAL CELLS

Journal Article AMERICAN JOURNAL OF PHYSIOLOGY · September 1, 1994 Link to item Cite

ISOLATION OF A GENOMIC CLONE THAT ENCODES A KIDNEY THROMBOXANE-A(2) (TXA(2)) RECEPTOR

Conference JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY · September 1, 1994 Link to item Cite

Leukotrienes in renal transplant rejection in rats. Distinct roles for leukotriene B4 and peptidoleukotrienes in the pathogenesis of allograft injury.

Journal Article J Immunol · January 15, 1994 To investigate the role of leukotrienes in renal allograft rejection, we studied the effects of specific leukotriene inhibitors in a rat kidney transplant model. The enhanced renal production of leukotrienes observed in allograft recipients was reduced in ... Link to item Cite

Improved renal function in mouse kidney allografts lacking MHC class I antigens.

Journal Article J Immunol · July 1, 1993 The immunological responses that lead to rejection of organ and tissue transplants are triggered by the recognition of proteins encoded within the MHC. The relative contributions of responses directed toward MHC class I compared with class II in the loss o ... Link to item Cite

Thromboxane binding and signal transduction in rat glomerular mesangial cells.

Journal Article Am J Physiol · February 1993 Thromboxane A2 (TxA2) stimulates contraction of glomerular mesangial cells. However, mesangial cell TxA2 receptors have not been previously characterized. We therefore investigated TxA2 binding and TxA2-associated signal transduction pathways in rat glomer ... Full text Link to item Cite

Characterization of glomerular thromboxane receptors in murine lupus nephritis.

Journal Article J Pharmacol Exp Ther · February 1993 Renal thromboxane (Tx) production is increased in the MRL-lpr murine model of lupus nephritis. To investigate the relationship between increased Tx production and number and affinity of Tx receptors, we measured binding of the Tx receptor antagonist [3H][S ... Link to item Cite

Thromboxane augmentation of alloreactive T cell function.

Journal Article Transplantation · September 1992 Thromboxane (Tx) plays a vital role in the dysfunction and ultimate rejection of MHC-disparate renal allografts. In addition to its potent vasoconstrictory properties, in vivo studies have implied that Tx is capable of promoting immune cytotoxic T cell fun ... Full text Link to item Cite

Effect of anti-CD4 antibody treatment on inflammatory arthritis in MRL-lpr/lpr mice.

Journal Article Clin Immunol Immunopathol · August 1992 MRL-lpr/lpr mice develop an inflammatory arthritis in association with other manifestations of autoimmunity. Although a variety of immune cell disturbances have been described in these mice, the relationship of these abnormalities to the pathogenesis of ar ... Full text Link to item Cite

Thromboxane receptor blockade reduces renal injury in murine lupus nephritis.

Journal Article Kidney Int · April 1992 To investigate the role of thromboxane A2 (TxA2) in murine lupus, we assessed the effects of the specific thromboxane receptor antagonist GR32191 on immune complex glomerulonephritis in MRL-lpr/lpr mice. Forty mg/kg/day GR32191 was given by twice daily sub ... Full text Link to item Cite

Physiologic role for enhanced renal thromboxane production in murine lupus nephritis.

Journal Article Prostaglandins · July 1991 To investigate the physiologic significance of enhanced renal thromboxane production in murine lupus nephritis, we measured renal hemodynamics and eicosanoid production in MRL-lpr/lpr mice from 8 to 20 weeks of age. Over this age range, MRL-lpr/lpr mice de ... Full text Link to item Cite

Acute renal failure in critically ill patients: prognosis for recovery of kidney function after prolonged dialysis support.

Journal Article Crit Care Med · January 1991 OBJECTIVE: To clarify the prognosis for eventual recovery of kidney function in patients who experience prolonged dialysis dependence after acute renal failure (ARF). DESIGN: Retrospective, chart review. SETTING: Inpatients of a large, referral-based hospi ... Full text Link to item Cite

Enhanced renal leukotriene production in murine lupus: role of lipoxygenase metabolites.

Journal Article Kidney Int · January 1991 To investigate the potential role of leukotrienes in murine lupus, we measured renal hemodynamics and renal leukotriene production in MRL-lpr/lpr mice at 12 and 20 weeks of age. Over this age range, these animals develop overt manifestations of autoimmune ... Full text Link to item Cite

Thromboxane receptor blockade improves cyclosporine nephrotoxicity in rats.

Journal Article Prostaglandins · February 1990 Cyclosporine A (CyA) nephrotoxicity is associated with impaired renal hemodynamic function and increased production of the vasoconstrictor eicosanoid thromboxane A2 (TxA2). In CyA toxic rats, renal dysfunction can be partially reversed by inhibitors of thr ... Full text Link to item Cite

Immature omental teratoma.

Journal Article Arch Pathol Lab Med · August 1987 Immature omental teratomas are extremely rare neoplasms. To our knowledge, only two cases have been reported in the literature. In some anatomic locations, the malignant potential of immature teratomas correlates with the presence and quantity of neuroecto ... Link to item Cite