title: Glomerular endothelial cell injury and cross talk in diabetic kidney disease.
abstract: Diabetic kidney disease (DKD) remains a leading cause of new-onset end-stage renal disease (ESRD), and yet, at present, the treatment is still very limited. A better understanding of the pathogenesis of DKD is therefore necessary to develop more effective therapies. Increasing evidence suggests that glomerular endothelial cell (GEC) injury plays a major role in the development and progression of DKD. Alteration of the glomerular endothelial cell surface layer, including its major component, glycocalyx, is a leading cause of microalbuminuria observed in early DKD. Many studies suggest a presence of cross talk between glomerular cells, such as between GEC and mesangial cells or GEC and podocytes. PDGFB/PDGFRβ is a major mediator for GEC and mesangial cell cross talk, while vascular endothelial growth factor (VEGF), angiopoietins, and endothelin-1 are the major mediators for GEC and podocyte communication. In DKD, GEC injury may lead to podocyte damage, while podocyte loss further exacerbates GEC injury, forming a vicious cycle. Therefore, GEC injury may predispose to albuminuria in diabetes either directly or indirectly by communication with neighboring podocytes and mesangial cells via secreted mediators. Identification of novel mediators of glomerular cell cross talk, such as microRNAs, will lead to a better understanding of the pathogenesis of DKD. Targeting these mediators may be a novel approach to develop more effective therapy for DKD.
authors.affiliation: Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu, China; and.
authors.forename: Jia
authors.initials: J
authors.lastname: Fu
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Kyung
authors.initials: K
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Chuang
authors.affiliation: Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu, China; and.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York cijiang.he@mssm.edu.
authors.forename: John Cijiang
authors.initials: JC
authors.lastname: He
mesh_terms: D000419:Albuminuria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002450:Cell Communication; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000098:blood supply*; D050527:Mesangial Cells / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs
keywords: angiopoietin; diabetes; endothelial cells; endothelial nitric oxide; endothelial surface layer; endothelin-1; fenestrate; glomerular filtration barrier; glycocalyx; hepatocyte growth factor; insulin-like growth factor; microRNA; prostanoids; proteoglycans; vascular endothelial growth factor