Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Apoptosis in podocytes induced by TGF-β and Smad7
Mario Schiffer, … , Peter Mundel, Erwin P. Böttinger
Mario Schiffer, … , Peter Mundel, Erwin P. Böttinger
Published September 15, 2001
Citation Information: J Clin Invest. 2001;108(6):807-816. https://doi.org/10.1172/JCI12367.
View: Text | PDF
Article

Apoptosis in podocytes induced by TGF-β and Smad7

  • Text
  • PDF
Abstract

Primary and secondary forms of focal segmental glomerulosclerosis (FSGS) are characterized by depletion of podocytes and constitute a central manifestation of chronic progressive glomerular diseases. Here we report that podocytes undergo apoptosis at early stages in the course of progressive glomerulosclerosis in TGF-β1 transgenic mice. Apoptosis is associated with progressive depletion of podocytes and precedes mesangial expansion. Smad7 protein expression is strongly induced specifically in damaged podocytes of transgenic mice and in cultured murine podocytes treated with TGF-β. TGF-β1 and Smad7 each induce apoptosis in podocytes, and their coexpression has an additive effect. Activation of p38 MAP kinase and caspase-3 is required for TGF-β–mediated apoptosis, but not for apoptosis induced by Smad7. Unlike TGF-β, Smad7 inhibits nuclear translocation and transcriptional activity of the cell survival factor NF-κB. Our results suggest a novel functional role for Smad7 as amplifier of TGF-β−induced apoptosis in podocytes and a new pathomechanism for podocyte depletion in progressive glomerulosclerosis.

Authors

Mario Schiffer, Markus Bitzer, Ian S.D. Roberts, Jeffrey B. Kopp, Peter ten Dijke, Peter Mundel, Erwin P. Böttinger

×
Options: View larger image (or click on image) Download as PowerPoint
Summary of analyses of cell counts and surface areas in glomerular sections

Summary of analyses of cell counts and surface areas in glomerular sections


Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts