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Tomokazu Souma

Assistant Professor in Medicine
Medicine, Nephrology

Selected Publications


AXL inhibition suppresses early allograft monocyte-to-macrophage differentiation and prolongs allograft survival.

Conference JCI Insight · March 8, 2024 Innate immune cells are important in the initiation and potentiation of alloimmunity in transplantation. Immediately upon organ anastomosis and reperfusion, recipient monocytes enter the graft from circulation and differentiate to inflammatory macrophages ... Full text Link to item Cite

Transitional cell states sculpt tissue topology during lung regeneration.

Journal Article Cell Stem Cell · November 2, 2023 Organ regeneration requires dynamic cell interactions to reestablish cell numbers and tissue architecture. While we know the identity of progenitor cells that replace lost tissue, the transient states they give rise to and their role in repair remain elusi ... Full text Link to item Cite

Divergent Actions of Renal Tubular and Endothelial Type 1 IL-1 Receptor Signaling in Toxin-Induced AKI.

Journal Article J Am Soc Nephrol · October 1, 2023 SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney pro ... Full text Link to item Cite

A macrophage-endothelial immunoregulatory axis ameliorates septic acute kidney injury.

Journal Article Kidney Int · March 2023 The most common cause of acute kidney injury (AKI) in critically ill patients is sepsis. Kidney macrophages consist of both F4/80hi and CD11bhi cells. The role of macrophage subpopulations in septic AKI pathogenesis remains unclear. As F4/80hi macrophages ... Full text Link to item Cite

Sex differences in resilience to ferroptosis underlie sexual dimorphism in kidney injury and repair.

Journal Article Cell Rep · November 8, 2022 In both humans and mice, repair of acute kidney injury is worse in males than in females. Here, we provide evidence that this sexual dimorphism results from sex differences in ferroptosis, an iron-dependent, lipid-peroxidation-driven regulated cell death. ... Full text Open Access Link to item Cite

Stromal Transcription Factor 21 Regulates Development of the Renal Stroma via Interaction with Wnt/β-Catenin Signaling.

Journal Article Kidney360 · July 28, 2022 BACKGROUND: Kidney formation requires coordinated interactions between multiple cell types. Input from the interstitial progenitor cells is implicated in multiple aspects of kidney development. We previously reported that transcription factor 21 (Tcf21) is ... Full text Link to item Cite

Type 1 Angiotensin Receptors on CD11c-Expressing Cells Protect Against Hypertension by Regulating Dendritic Cell-Mediated T Cell Activation.

Journal Article Hypertension · June 2022 BACKGROUND: Type 1 angiotensin (AT1) receptors are expressed on immune cells, and we previously found that bone marrow-derived AT1 receptors protect against Ang (angiotensin) II-induced hypertension. CD11c is expressed on myeloid cells derived from the bon ... Full text Link to item Cite

In Vivo Assessment of Ferroptosis and Ferroptotic Stress in Mice.

Journal Article Curr Protoc · April 2022 Ferroptosis is iron-dependent, lipid peroxidation-driven, regulated cell death that is triggered when cellular glutathione peroxidase 4 (GPX4)-mediated cellular defense is insufficient to prevent pathologic accumulation of toxic lipid peroxides. Ferroptosi ... 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

Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair.

Journal Article Elife · July 19, 2021 Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, ... Full text Open Access Link to item Cite

Hypoxia signaling in renal pericytes-is it safe to activate?

Journal Article Kidney Int · June 2021 While excitement has grown for the use of hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors for treating renal anemia, multiple preclinical studies have shown the complex and cell-type-dependent roles of HIFs in kidney disease pathogenesis, incl ... Full text Link to item Cite

Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair

Journal Article · 2021 Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, ... Full text Cite

SVEP1 as a Genetic Modifier of TEK-Related Primary Congenital Glaucoma.

Journal Article Invest Ophthalmol Vis Sci · October 1, 2020 PURPOSE: Affecting children by age 3, primary congenital glaucoma (PCG) can cause debilitating vision loss by the developmental impairment of aqueous drainage resulting in high intraocular pressure (IOP), globe enlargement, and optic neuropathy. TEK haploi ... Full text Open Access Link to item Cite

Yolk-sac-derived macrophages progressively expand in the mouse kidney with age.

Journal Article Elife · April 17, 2020 Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, angiogenes ... Full text Link to item Cite

Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair.

Journal Article Nat Cell Biol · January 2020 Osteoclasts are multinucleated cells of the monocyte/macrophage lineage that degrade bone. Here, we used lineage tracing studies-labelling cells expressing Cx3cr1, Csf1r or Flt3-to identify the precursors of osteoclasts in mice. We identified an erythromye ... Full text Link to item Cite

SVEP1 as a genetic modifier of TEK-related primary congenital glaucoma

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2020 Cite

Yolk-Sac-Derived Macrophages Progressively Expand in the Mouse Kidney with Age

Journal Article · October 21, 2019 Abstract Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, a ... Full text Cite

Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma.

Journal Article Elife · October 17, 2019 Elevated intraocular pressure (IOP) due to insufficient aqueous humor outflow through the trabecular meshwork and Schlemm's canal (SC) is the most important risk factor for glaucoma, a leading cause of blindness worldwide. We previously reported loss of fu ... Full text Link to item Cite

FGFR4 does not contribute to progression of chronic kidney disease.

Journal Article Sci Rep · October 1, 2019 In chronic kidney disease (CKD), elevated serum levels of the phosphate regulating hormone fibroblast growth factor (FGF) 23 have emerged as powerful risk factors for cardiovascular disease and death. Mechanistically, FGF23 can bind and activate fibroblast ... Full text Link to item Cite

Targeting VE-PTP phosphatase protects the kidney from diabetic injury.

Journal Article J Exp Med · April 1, 2019 Diabetic nephropathy is a leading cause of end-stage kidney failure. Reduced angiopoietin-TIE2 receptor tyrosine kinase signaling in the vasculature leads to increased vascular permeability, inflammation, and endothelial cell loss and is associated with th ... Full text Link to item Cite

AXL inhibition suppresses early allograft monocyte-to-macrophage differentiation and prolongs allograft survival.

Conference JCI Insight · March 8, 2024 Innate immune cells are important in the initiation and potentiation of alloimmunity in transplantation. Immediately upon organ anastomosis and reperfusion, recipient monocytes enter the graft from circulation and differentiate to inflammatory macrophages ... Full text Link to item Cite

Transitional cell states sculpt tissue topology during lung regeneration.

Journal Article Cell Stem Cell · November 2, 2023 Organ regeneration requires dynamic cell interactions to reestablish cell numbers and tissue architecture. While we know the identity of progenitor cells that replace lost tissue, the transient states they give rise to and their role in repair remain elusi ... Full text Link to item Cite

Divergent Actions of Renal Tubular and Endothelial Type 1 IL-1 Receptor Signaling in Toxin-Induced AKI.

Journal Article J Am Soc Nephrol · October 1, 2023 SIGNIFICANCE STATEMENT: Activation of the type 1 IL-1 receptor (IL-1R1) triggers a critical innate immune signaling cascade that contributes to the pathogenesis of AKI. However, blockade of IL-1 signaling in AKI has not consistently demonstrated kidney pro ... Full text Link to item Cite

A macrophage-endothelial immunoregulatory axis ameliorates septic acute kidney injury.

Journal Article Kidney Int · March 2023 The most common cause of acute kidney injury (AKI) in critically ill patients is sepsis. Kidney macrophages consist of both F4/80hi and CD11bhi cells. The role of macrophage subpopulations in septic AKI pathogenesis remains unclear. As F4/80hi macrophages ... Full text Link to item Cite

Sex differences in resilience to ferroptosis underlie sexual dimorphism in kidney injury and repair.

Journal Article Cell Rep · November 8, 2022 In both humans and mice, repair of acute kidney injury is worse in males than in females. Here, we provide evidence that this sexual dimorphism results from sex differences in ferroptosis, an iron-dependent, lipid-peroxidation-driven regulated cell death. ... Full text Open Access Link to item Cite

Stromal Transcription Factor 21 Regulates Development of the Renal Stroma via Interaction with Wnt/β-Catenin Signaling.

Journal Article Kidney360 · July 28, 2022 BACKGROUND: Kidney formation requires coordinated interactions between multiple cell types. Input from the interstitial progenitor cells is implicated in multiple aspects of kidney development. We previously reported that transcription factor 21 (Tcf21) is ... Full text Link to item Cite

Type 1 Angiotensin Receptors on CD11c-Expressing Cells Protect Against Hypertension by Regulating Dendritic Cell-Mediated T Cell Activation.

Journal Article Hypertension · June 2022 BACKGROUND: Type 1 angiotensin (AT1) receptors are expressed on immune cells, and we previously found that bone marrow-derived AT1 receptors protect against Ang (angiotensin) II-induced hypertension. CD11c is expressed on myeloid cells derived from the bon ... Full text Link to item Cite

In Vivo Assessment of Ferroptosis and Ferroptotic Stress in Mice.

Journal Article Curr Protoc · April 2022 Ferroptosis is iron-dependent, lipid peroxidation-driven, regulated cell death that is triggered when cellular glutathione peroxidase 4 (GPX4)-mediated cellular defense is insufficient to prevent pathologic accumulation of toxic lipid peroxides. Ferroptosi ... 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

Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair.

Journal Article Elife · July 19, 2021 Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, ... Full text Open Access Link to item Cite

Hypoxia signaling in renal pericytes-is it safe to activate?

Journal Article Kidney Int · June 2021 While excitement has grown for the use of hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors for treating renal anemia, multiple preclinical studies have shown the complex and cell-type-dependent roles of HIFs in kidney disease pathogenesis, incl ... Full text Link to item Cite

Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair

Journal Article · 2021 Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, ... Full text Cite

SVEP1 as a Genetic Modifier of TEK-Related Primary Congenital Glaucoma.

Journal Article Invest Ophthalmol Vis Sci · October 1, 2020 PURPOSE: Affecting children by age 3, primary congenital glaucoma (PCG) can cause debilitating vision loss by the developmental impairment of aqueous drainage resulting in high intraocular pressure (IOP), globe enlargement, and optic neuropathy. TEK haploi ... Full text Open Access Link to item Cite

Yolk-sac-derived macrophages progressively expand in the mouse kidney with age.

Journal Article Elife · April 17, 2020 Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, angiogenes ... Full text Link to item Cite

Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair.

Journal Article Nat Cell Biol · January 2020 Osteoclasts are multinucleated cells of the monocyte/macrophage lineage that degrade bone. Here, we used lineage tracing studies-labelling cells expressing Cx3cr1, Csf1r or Flt3-to identify the precursors of osteoclasts in mice. We identified an erythromye ... Full text Link to item Cite

SVEP1 as a genetic modifier of TEK-related primary congenital glaucoma

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2020 Cite

Yolk-Sac-Derived Macrophages Progressively Expand in the Mouse Kidney with Age

Journal Article · October 21, 2019 Abstract Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, a ... Full text Cite

Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma.

Journal Article Elife · October 17, 2019 Elevated intraocular pressure (IOP) due to insufficient aqueous humor outflow through the trabecular meshwork and Schlemm's canal (SC) is the most important risk factor for glaucoma, a leading cause of blindness worldwide. We previously reported loss of fu ... Full text Link to item Cite

FGFR4 does not contribute to progression of chronic kidney disease.

Journal Article Sci Rep · October 1, 2019 In chronic kidney disease (CKD), elevated serum levels of the phosphate regulating hormone fibroblast growth factor (FGF) 23 have emerged as powerful risk factors for cardiovascular disease and death. Mechanistically, FGF23 can bind and activate fibroblast ... Full text Link to item Cite

Targeting VE-PTP phosphatase protects the kidney from diabetic injury.

Journal Article J Exp Med · April 1, 2019 Diabetic nephropathy is a leading cause of end-stage kidney failure. Reduced angiopoietin-TIE2 receptor tyrosine kinase signaling in the vasculature leads to increased vascular permeability, inflammation, and endothelial cell loss and is associated with th ... Full text Link to item Cite

Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development.

Journal Article J Am Soc Nephrol · December 2018 BACKGROUND: The mammalian kidney develops through reciprocal inductive signals between the metanephric mesenchyme and ureteric bud. Transcription factor 21 (Tcf21) is highly expressed in the metanephric mesenchyme, including Six2-expressing cap mesenchyme ... Full text Link to item Cite

Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health: A Scoping Review.

Journal Article Clin J Am Soc Nephrol · October 8, 2018 BACKGROUND AND OBJECTIVES: Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact of PFAS exposure on human health is not well understood, and ... Full text Link to item Cite

Novel ACE2-Fc chimeric fusion provides long-lasting hypertension control and organ protection in mouse models of systemic renin angiotensin system activation.

Journal Article Kidney Int · July 2018 Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that potently degrades angiotensin II to angiotensin 1-7. Previous studies showed that injection of the enzymatic ectodomain of recombinant ACE2 (rACE2) markedly increases circulatory levels of A ... Full text Open Access Link to item Cite

Acute kidney injury to chronic kidney disease transition: insufficient cellular stress response.

Journal Article Curr Opin Nephrol Hypertens · July 2018 Featured Publication PURPOSE OF REVIEW: Recent epidemiological and preclinical mechanistic studies provide strong evidence that acute kidney injury (AKI) and chronic kidney disease (CKD) form an interconnected syndrome. Injured kidneys undergo a coordinated reparative process ... Full text Open Access Link to item Cite

Context-dependent functions of angiopoietin 2 are determined by the endothelial phosphatase VEPTP.

Journal Article Proc Natl Acad Sci U S A · February 6, 2018 Featured Publication The angiopoietin (ANGPT)-TIE2/TEK signaling pathway is essential for blood and lymphatic vascular homeostasis. ANGPT1 is a potent TIE2 activator, whereas ANGPT2 functions as a context-dependent agonist/antagonist. In disease, ANGPT2-mediated inhibition of ... Full text Open Access Link to item Cite

Angiopoietin-1 is required for Schlemm's canal development in mice and humans.

Journal Article J Clin Invest · December 1, 2017 Featured Publication Primary congenital glaucoma (PCG) is a leading cause of blindness in children worldwide and is caused by developmental defects in 2 aqueous humor outflow structures, Schlemm's canal (SC) and the trabecular meshwork. We previously identified loss-of-functio ... Full text Open Access Link to item Cite

Personalized Peptide Arrays for Detection of HLA Alloantibodies in Organ Transplantation.

Journal Article J Vis Exp · September 6, 2017 In organ transplantation, the function and longevity of the graft critically rely on the success of controlling immunological rejection reactivity against human leukocyte antigens (HLA). Histocompatibility guidelines are based on laboratory tests of anti-H ... Full text Link to item Cite

Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model and improves maternal and fetal outcomes.

Journal Article Sci Signal · May 16, 2017 Featured Publication Placental activation of the renin-angiotensin system (RAS) plays a key role in the pathogenesis of preeclampsia. Reactive oxygen species (ROS) are thought to affect placental angiogenesis, which is critical for preventing preeclampsia pathology. We examine ... Full text Open Access Link to item Cite

A Fluorometric Method of Measuring Carboxypeptidase Activities for Angiotensin II and Apelin-13.

Journal Article Sci Rep · April 5, 2017 Degradation of the biologically potent octapeptide angiotensin Ang II-(1-8) is mediated by the activities of several peptidases. The conversion of Ang II to the septapeptide Ang-(1-7) is of particular interest as the latter also confers organ protection. T ... Full text Link to item Cite

Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression.

Journal Article Kidney Int · February 2017 Featured Publication Acute kidney injury is a devastating disease with high morbidity in hospitalized patients and contributes to the pathogenesis of chronic kidney disease. An underlying mechanism of acute kidney injury involves ischemia-reperfusion injury which, in turn, ind ... Full text Open Access Link to item Cite

A Novel Method for Anti-HLA Antibody Detection Using Personalized Peptide Arrays.

Journal Article Transplant Direct · November 2016 BACKGROUND: HLA mismatches are the primary cause of alloantibody-mediated rejection (AMR) in organ transplantation. To delineate antigenic and immunogenic potentials among individual HLA mismatches, information regarding antibody specificity at the epitope ... Full text Link to item Cite

Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity.

Journal Article J Clin Invest · July 1, 2016 Featured Publication Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); howev ... Full text Open Access Link to item Cite

Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia Signaling.

Journal Article J Am Soc Nephrol · February 2016 Featured Publication Erythropoietin (Epo) is produced by renal Epo-producing cells (REPs) in a hypoxia-inducible manner. The conversion of REPs into myofibroblasts and coincident loss of Epo-producing ability are the major cause of renal fibrosis and anemia. However, the hypox ... Full text Link to item Cite

Hypoxia Signaling Cascade for Erythropoietin Production in Hepatocytes.

Journal Article Mol Cell Biol · August 2015 Erythropoietin (Epo) is produced in the kidney and liver in a hypoxia-inducible manner via the activation of hypoxia-inducible transcription factors (HIFs) to maintain oxygen homeostasis. Accelerating Epo production in hepatocytes is one plausible therapeu ... Full text Link to item Cite

Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets.

Journal Article Cell · May 21, 2015 Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-seq ... Full text Link to item Cite

Renal erythropoietin-producing cells in health and disease.

Journal Article Front Physiol · 2015 Featured Publication Erythropoietin (Epo) is an indispensable erythropoietic hormone primarily produced from renal Epo-producing cells (REPs). Epo production in REPs is tightly regulated in a hypoxia-inducible manner to maintain tissue oxygen homeostasis. Insufficient Epo prod ... Full text Link to item Cite

[Renal fibrosis and anemia].

Journal Article Nihon Jinzo Gakkai Shi · 2015 Link to item Cite

Renal fibrosis and anemia

Journal Article Japanese Journal of Nephrology · January 1, 2015 Open Access Cite

[Renal erythropoietin-producing cells and kidney disease].

Journal Article Nihon Rinsho · September 2014 Erythropoietin(EPO) is an indispensable erythropoietic hormone, produced mainly from kidneys in adult, and the production declines with progression of chronic kidney disease(CKD). Renal EPO-producing cells(REPs) are peri-tubular interstitial fibroblasts. D ... Link to item Cite

GATA2 regulates body water homeostasis through maintaining aquaporin 2 expression in renal collecting ducts.

Journal Article Mol Cell Biol · June 2014 The transcription factor GATA2 plays pivotal roles in early renal development, but its distribution and physiological functions in adult kidney are largely unknown. We examined the GATA2 expression pattern in the adult kidney by tracing green fluorescent p ... Full text Link to item Cite

Plasticity of renal erythropoietin-producing cells governs fibrosis.

Journal Article J Am Soc Nephrol · October 2013 Featured Publication CKD progresses with fibrosis and erythropoietin (Epo)-dependent anemia, leading to increased cardiovascular complications, but the mechanisms linking Epo-dependent anemia and fibrosis remain unclear. Here, we show that the cellular phenotype of renal Epo-p ... Full text Link to item Cite

Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3.

Journal Article PLoS One · 2013 The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremi ... Full text Link to item Cite

A mouse model of adult-onset anaemia due to erythropoietin deficiency.

Journal Article Nat Commun · 2013 Erythropoietin regulates erythropoiesis in a hypoxia-inducible manner. Here we generate inherited super-anaemic mice (ISAM) as a mouse model of adult-onset anaemia caused by erythropoietin deficiency. ISAM express erythropoietin in the liver but lack eryth ... Full text Link to item Cite

UG4 enhancer-driven GATA-2 and bone morphogenetic protein 4 complementation remedies the CAKUT phenotype in Gata2 hypomorphic mutant mice.

Journal Article Mol Cell Biol · June 2012 During renal development, the proper emergence of the ureteric bud (UB) from the Wolffian duct is essential for formation of the urinary system. Previously, we showed that expression of transcription factor GATA-2 in the urogenital primordium was demarcate ... Full text Link to item Cite

Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation.

Journal Article Biochem J · April 1, 2012 Abnormal cellular accumulation of the dicarbonyl metabolite MG (methylglyoxal) occurs on exposure to high glucose concentrations, inflammation, cell aging and senescence. It is associated with increased MG-adduct content of protein and DNA linked to increa ... Full text Link to item Cite

Luminal alkalinization attenuates proteinuria-induced oxidative damage in proximal tubular cells.

Journal Article J Am Soc Nephrol · April 2011 A highly acidic environment surrounds proximal tubular cells as a result of their reabsorption of HCO(3)(-). It is unclear whether this luminal acidity affects proteinuria-induced progression of tubular cell damage. Here, we investigated the contribution o ... Full text Link to item Cite

Methylglyoxal augments intracellular oxidative stress in human aortic endothelial cells.

Journal Article Free Radic Res · January 2010 Methylglyoxal (MGO) is a non-enzymatic metabolite in the glycolytic pathway and its concentration in blood and tissues is elevated in diabetes and renal failure. MGO induces tissue injuries via ROS; however, the mechanism remains to be clarified. The prese ... Full text Link to item Cite

The HMG-CoA reductase inhibitor pravastatin stimulates insulin secretion through organic anion transporter polypeptides.

Journal Article Drug Metab Pharmacokinet · 2010 The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin has been reported to have a beneficial effect on reducing the new onset of diabetes as well as lowering plasma lipids. Because pravastatin is a water-soluble organic anion, it cannot ... Full text Link to item Cite

SLCO4C1 transporter eliminates uremic toxins and attenuates hypertension and renal inflammation.

Journal Article J Am Soc Nephrol · December 2009 Hypertension in patients with chronic kidney disease (CKD) strongly associates with cardiovascular events. Among patients with CKD, reducing the accumulation of uremic toxins may protect against the development of hypertension and progression of renal dama ... Full text Link to item Cite

Antenatal Bartter's syndrome: why is this not a lethal condition?

Journal Article QJM · December 2008 There are four themes in this teaching exercise for Professor McCance. The first challenge was to explain how a premature infant with Bartter's syndrome could survive despite having such a severe degree of renal salt wasting. Second, the medical team wante ... Full text Link to item Cite