Glomerular endothelial cell injury and cross talk in diabetic kidney disease

Jia Fu, Kyung Lee, Peter Y. Chuang, Zhi Hong Liu, John Cijiang He

Research output: Contribution to journalReview articlepeer-review

201 Scopus citations

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/PDGFRß 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.

Original languageEnglish
Pages (from-to)F287-F297
JournalAmerican Journal of Physiology - Renal Physiology
Volume308
Issue number4
DOIs
StatePublished - 2015

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

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