The ER unfolded protein response effector, ATF6, reduces cardiac fibrosis and decreases activation of cardiac fibroblasts

Winston T. Stauffer, Erik A. Blackwood, Khalid Azizi, Randal J. Kaufman, Christopher C. Glembotski

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Activating transcription factor-6 α (ATF6) is one of the three main sensors and effectors of the endoplasmic reticulum (ER) stress response and, as such, it is critical for protecting the heart and other tissues from a variety of environmental insults and disease states. In the heart, ATF6 has been shown to protect cardiac myocytes. However, its roles in other cell types in the heart are unknown. Here we show that ATF6 decreases the activation of cardiac fibroblasts in response to the cytokine, transforming growth factor β (TGFβ), which can induce fibroblast trans‐differentiation into a myofibroblast phenotype through signaling via the TGFβ–Smad pathway. ATF6 activation suppressed fibroblast contraction and the induction of α smooth muscle actin (αSMA). Conversely, fibroblasts were hyperactivated when ATF6 was silenced or deleted. ATF6 thus represents a novel inhibitor of the TGFβ–Smad axis of cardiac fibroblast activation.

Original languageEnglish (US)
Article number1373
JournalInternational journal of molecular sciences
Volume21
Issue number4
DOIs
StatePublished - Feb 2 2020
Externally publishedYes

Keywords

  • ATF6
  • Cardiac fibroblast
  • Cardiac fibrosis
  • ER stress
  • Endoplasmic reticulum
  • Smad
  • TGFβ
  • UPR

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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