Skip to main content
padlock icon - secure page this page is secure

Transforming growth factor‐β/Smad signalling in diabetic nephropathy

Buy Article:

$52.00 + tax (Refund Policy)

Summary



Diabetic nephropathy (DN) is a major diabetic complication that is mediated by transforming growth factor (TGF)‐β1 via Smad‐dependent and ‐independent signalling pathways.


Under diabetic conditions, many profibrotic factors, such as advanced glycation end‐products and angiotensin II, can also activate the Smad signalling pathway via the extracellular signal‐regulated kinase/p38 mitogen‐activated protein kinase–Smad signalling cross‐talk pathway. Thus, Smads act as signal integrators and interact with other signalling pathways to mediate DN.


In the context of renal fibrosis, Smad3 is pathogenic, but Smad2 is protective. Deletion of Smad3 inhibits, whereas disruption of Smad2 upregulates, connective tissue growth factor and vascular endothelial growth factor expression and promotes both epithelial–myofibroblast and endothelial–myofibroblast transition.


Smad7 plays a protective role in DN because deletion of Smad7 enhances, whereas overexpression of Smad7 inhibits, Smad3‐mediated renal fibrosis and nuclear factor‐κB‐driven renal inflammation.


Transforming growth factor‐β1 activates Smad3 to regulate microRNAs that mediate renal fibrosis. Of these, miR‐21 and miR‐192 are upregulated, whereas the miR‐29 and miR‐200 families are downregulated.


Targeting downstream TGF‐β/Smad signalling by overexpressing Smad7‐ or Smad3‐dependent microRNA related to fibrosis may represent a novel and effective strategy for the treatment of DN.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Document Type: Research Article

Publication date: August 1, 2012

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more