Role of the JAK/STAT signaling pathway in diabetic nephropathy

Am J Physiol Renal Physiol. 2006 Apr;290(4):F762-8. doi: 10.1152/ajprenal.00181.2005.


Excessive cellular growth is a major contributor to pathological changes associated with diabetic nephropathy. In particular, high glucose-induced growth of glomerular mesangial cells is a characteristic feature of diabetes-induced renal complications. Glomerular mesangial cells respond to traditional growth factors, although in diabetes this occurs in the context of an environment enriched in both circulating vasoactive mediators and high glucose. For example, the vasoactive peptide ANG II has been implicated in the pathogenesis of diabetic renal disease, and recent findings suggest that high glucose and ANG II activate intracellular signaling processes, including the polyol pathway and generation of reactive oxygen species. These pathways activate the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling cascades in glomerular mesangial cells. Activation of the JAK/STAT signaling cascade can stimulate excessive proliferation and growth of glomerular mesangial cells, contributing to diabetic nephropathy. This review focuses on some of the key elements in the diabetic microenvironment, especially high glucose and the accumulation of advanced glycoxidation end products and considers their impact on ANG II and other vasoactive peptide-mediated signaling events in vitro and in vivo.

Publication types

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

MeSH terms

  • Angiotensin II / physiology
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / physiopathology*
  • Glucose / metabolism*
  • Glucose / pharmacokinetics
  • Humans
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiology
  • Protein-Tyrosine Kinases / metabolism*
  • STAT Transcription Factors / metabolism*
  • Signal Transduction*


  • STAT Transcription Factors
  • Angiotensin II
  • Protein-Tyrosine Kinases
  • Glucose