Inhibitors/antagonists of TGF-β system in kidney fibrosis

Nephrol Dial Transplant. 2012 Oct;27(10):3686-91. doi: 10.1093/ndt/gfs381.

Abstract

Renal fibrosis is a major hallmark of chronic kidney disease, regardless of the initial causes, and prominent renal fibrosis predicts poor prognosis for renal insufficiency. Transforming growth factor (TGF)-β plays a pivotal role in the progression of renal fibrosis, and therapeutic interventions targeting TGF-β have been successful and well tolerated in animal models. However, these interventions might have adverse effects by inducing systemic inflammation due to the strong bifunctional role of TGF-β (pro-fibrotic and anti-inflammatory). This review of the current literature focuses on the inhibitors/antagonists of TGF-β, and discusses possible therapeutic approaches targeting them, describing the effectiveness of orally active bone morphogenetic protein 7 mimetics in reversing established fibrosis. It will conclude with a brief discussion of possible future directions for research.

Publication types

  • Editorial
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 7 / agonists
  • Bone Morphogenetic Protein 7 / antagonists & inhibitors
  • Bone Morphogenetic Protein 7 / physiology
  • Fibrosis
  • Humans
  • Kidney / drug effects
  • Kidney / pathology*
  • Kidney / physiopathology
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology
  • Signal Transduction
  • Transforming Growth Factor alpha / antagonists & inhibitors*
  • Transforming Growth Factor alpha / physiology

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Transforming Growth Factor alpha