Renin-angiotensin system within the diabetic podocyte

Am J Physiol Renal Physiol. 2015 Jan 1;308(1):F1-10. doi: 10.1152/ajprenal.00531.2013. Epub 2014 Oct 22.

Abstract

Diabetic kidney disease is the leading cause of end-stage renal disease. Podocytes are differentiated cells necessary for the development and maintenance of the glomerular basement membrane and the capillary tufts, as well as the function of the glomerular filtration barrier. The epithelial glomerular cells express a local renin-angiotensin system (RAS) that varies in different pathological situations such as hyperglycemia or mechanical stress. RAS components have been shown to be altered in diabetic podocytopathy, and their modulation may modify diabetic nephropathy progression. Podocytes are a direct target for angiotensin II-mediated injury by altered expression and distribution of podocyte proteins. Furthermore, angiotensin II promotes podocyte injury indirectly by inducing cellular hypertrophy, increased apoptosis, and changes in the anionic charge of the glomerular basement membrane, among other effects. RAS blockade has been shown to decrease the level of proteinuria and delay the progression of chronic kidney disease. This review summarizes the local intraglomerular RAS and its imbalance in diabetic podocytopathy. A better understanding of the intrapodocyte RAS might provide a new approach for diabetic kidney disease treatment.

Keywords: ACE2; angiotensin II; podocytes; renin-angiotensin system.

Publication types

  • Review

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / metabolism*
  • Humans
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Podocytes / drug effects
  • Podocytes / metabolism*
  • Renin-Angiotensin System*

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Insulin
  • Angiotensin II