AI Article Synopsis
- ATF6 is a key player in the endoplasmic reticulum stress response, helping to protect the heart and other tissues from environmental stress and diseases.
- The study found that ATF6 reduces the activation of cardiac fibroblasts triggered by TGFβ, preventing their transformation into myofibroblasts.
- When ATF6 is silenced or deleted, fibroblasts become overly activated, suggesting that ATF6 acts as a new inhibitor in the TGFβ-Smad pathway of fibroblast activation.
Article 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073073 | PMC |
| http://dx.doi.org/10.3390/ijms21041373 | DOI Listing |
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