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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

Smad7 mediates transforming growth factor-beta-induced apoptosis in mesangial cells

Tomokazu Okado1, Yoshio Terada, Hiroyuki Tanaka

  • 1Homeostasis Medicine and Nephrology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

Kidney International
|September 18, 2002
PubMed
Abstract

Insights

Transforming growth factor-beta (TGF-beta) induces apoptosis in mesangial cells via Smad7 activation. Smad7, not Smad2 or Smad3, triggers caspase-3, leading to cell death, clarifying TGF-beta signaling pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Signaling Pathways

Background:

  • Transforming growth factor-beta (TGF-beta) is known to inhibit cell growth and induce apoptosis.
  • Smad proteins are key downstream effectors of TGF-beta signaling, with Smad7 acting as a negative feedback regulator.
  • The specific role of Smad proteins in TGF-beta-induced apoptosis within mesangial cells remained unclear.

Purpose of the Study:

  • To investigate the function of Smad proteins in TGF-beta-induced apoptosis in mesangial cells.
  • To examine the effect of Smad overexpression on apoptosis using adenoviral vectors.
  • To elucidate the specific Smad proteins involved in this apoptotic pathway.

Main Methods:

  • Primary rat mesangial cells were utilized.
  • Smad7 promoter activity was assessed using a luciferase assay after transfection with a Smad7-promoter-luciferase-plasmid.
  • Apoptosis was induced by TGF-beta and Smad7 overexpression (AdCMV-Smad7) and measured via cell death ELISA, caspase-3 assay, and DNA laddering.

Main Results:

  • TGF-beta significantly upregulated Smad7 protein expression and promoter activity in mesangial cells.
  • Overexpression of Smad7 led to DNA fragmentation and increased apoptosis, as evidenced by cell death ELISA and caspase-3 activity.
  • In contrast, Smad2 and Smad3 overexpression did not significantly increase caspase-3 activity. Antisense oligonucleotide to Smad7 blocked TGF-beta-induced apoptosis.

Conclusions:

  • TGF-beta-induced apoptosis in mesangial cells is mediated by Smad7 activation of caspase-3.
  • Smad2 and Smad3 do not appear to play a direct role in this specific apoptotic mechanism.
  • These findings clarify the role of Smad7 in TGF-beta signaling within mesangial cells, highlighting its pro-apoptotic function.

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