Journal ArticleJ Clin Invest · December 17, 2024
Vitamin D regulates mineral homeostasis. The most biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), is synthesized by CYP27B1 from 25-dihydroxyvitamin D (25D) and inactivated by CYP24A1. Human monogenic diseases and genome-wide associ ...
Full textLink to itemCite
ConferenceJCI 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 textLink to itemCite
Journal ArticleCell 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleKidney 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 textLink to itemCite
Journal ArticleCell 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 textOpen AccessLink to itemCite
Journal ArticleKidney360 · 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 textLink to itemCite
Journal ArticleHypertension · 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 textLink to itemCite
Journal ArticleCurr 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 textLink to itemCite
Journal ArticleJCI 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 textLink to itemCite
Journal ArticleElife · 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 textOpen AccessLink to itemCite
Journal ArticleKidney 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 textLink to itemCite
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 textCite
Journal ArticleInvest 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 textOpen AccessLink to itemCite
Journal ArticleElife · 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 textLink to itemCite
Journal ArticleNat 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 textLink to itemCite
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 textCite
Journal ArticleElife · 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 textLink to itemCite
Journal ArticleSci 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleClin 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 textLink to itemCite
Journal ArticleKidney 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 textOpen AccessLink to itemCite
Journal ArticleCurr 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 textOpen AccessLink to itemCite
Journal ArticleProc 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 textOpen AccessLink to itemCite
Journal ArticleJ 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 textOpen AccessLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleSci 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 textOpen AccessLink to itemCite
Journal ArticleSci 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 textLink to itemCite
Journal ArticleKidney 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 textOpen AccessLink to itemCite
Journal ArticleTransplant 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 textLink to itemCite
Journal ArticleJ 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 textOpen AccessLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleMol 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 textLink to itemCite
Journal ArticleCell · 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 textLink to itemCite
Journal ArticleFront 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 textLink to itemCite
Journal ArticleNihon 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 itemCite
Journal ArticleMol 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticlePLoS 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 textLink to itemCite
Journal ArticleNat 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 textLink to itemCite
Journal ArticleMol 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 textLink to itemCite
Journal ArticleBiochem 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleFree 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 textLink to itemCite
Journal ArticleDrug 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 textLink to itemCite
Journal ArticleJ 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 textLink to itemCite
Journal ArticleQJM · 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 textLink to itemCite