Glomerular Endothelial Cell Injury and Cross Talk in Diabetic Kidney Disease

Am J Physiol Renal Physiol. 2015 Feb 15;308(4):F287-97. doi: 10.1152/ajprenal.00533.2014. Epub 2014 Nov 19.

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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Albuminuria / metabolism
  • Albuminuria / pathology
  • Albuminuria / physiopathology
  • Animals
  • Cell Communication*
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Kidney Glomerulus / blood supply*
  • Mesangial Cells / metabolism*
  • Mesangial Cells / pathology
  • MicroRNAs / metabolism
  • Podocytes / metabolism*
  • Podocytes / pathology
  • Signal Transduction*

Substances

  • Intercellular Signaling Peptides and Proteins
  • MicroRNAs