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Updated: Aug 25, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Bone morphogenetic protein-7 signals opposing transforming growth factor beta in mesangial cells

Shinong Wang1, Raimund Hirschberg

  • 1Harbor-UCLA Research and Education Institute, UCLA, Torrance, California 90502, USA.

The Journal of Biological Chemistry
|March 30, 2004
PubMed

Insights

Bone morphogenetic protein-7 (BMP7) opposes kidney fibrosis by inhibiting transforming growth factor beta (TGF-β) signaling. This study reveals BMP7 utilizes Smad5 and Smad6 to block TGF-β-induced fibrogenesis in mesangial cells.

Area of Science:

  • Nephrology
  • Cell Biology
  • Molecular Biology

Background:

  • Bone morphogenetic protein-7 (BMP7) is present in adult kidneys and mitigates renal fibrogenesis in rodent models.
  • BMP7 inhibits transforming growth factor beta (TGF-β)-driven fibrosis in mesangial cells by affecting matrix degradation and PAI-1 regulation.

Purpose of the Study:

  • To elucidate the signaling pathways and mechanisms by which BMP7 counteracts TGF-β actions in mesangial cells.
  • To investigate the role of Smad proteins in BMP7's anti-fibrotic effects.

Main Methods:

  • Utilized mesangial cells to study BMP7 and TGF-β signaling.
  • Performed Smad5 knockdown experiments.
  • Assessed transcriptional activation using CAGA-lux reporter assays.
  • Measured PAI-1 levels and nuclear Smad accumulation.

Main Results:

  • BMP7 reduced nuclear Smad3 accumulation and blocked TGF-β-induced CAGA-lux activation.
  • Smad5 knockdown impaired BMP7's ability to inhibit TGF-β-induced CAGA-lux activation and PAI-1 accumulation.
  • Smad5 knockdown reduced BMP7-induced Smad6 expression.
  • Forced expression of Smad5 or Smad6 mimicked BMP7's inhibitory effects on TGF-β-induced PAI-1 activation and secretion.

Conclusions:

  • A model is proposed where BMP7 opposes TGF-β-dependent mesangial fibrogenesis via Smad5 and the downstream inhibitory Smad6.
  • BMP7 reduces nuclear Smad3 availability and requires Smad5 signaling.
  • BMP7's mechanism does not involve Erk1/2, p38, JNK, Ski, or SnoN in mesangial cells.

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