{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:17:51Z","timestamp":1779311871568,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000850","name":"National Heart and Lung Institute","doi-asserted-by":"publisher","award":["1F31HL140850, R01HL135893, R01 HL75573, and R01 HL104535"],"award-info":[{"award-number":["1F31HL140850, R01HL135893, R01 HL75573, and R01 HL104535"]}],"id":[{"id":"10.13039\/501100000850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Activating transcription factor-6 \u03b1 (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 \u03b2 (TGF\u03b2), which can induce fibroblast trans-differentiation into a myofibroblast phenotype through signaling via the TGF\u03b2\u2013Smad pathway. ATF6 activation suppressed fibroblast contraction and the induction of \u03b1 smooth muscle actin (\u03b1SMA). Conversely, fibroblasts were hyperactivated when ATF6 was silenced or deleted. ATF6 thus represents a novel inhibitor of the TGF\u03b2\u2013Smad axis of cardiac fibroblast activation.<\/jats:p>","DOI":"10.3390\/ijms21041373","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T04:06:01Z","timestamp":1582085161000},"page":"1373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The ER Unfolded Protein Response Effector, ATF6, Reduces Cardiac Fibrosis and Decreases Activation of Cardiac Fibroblasts"],"prefix":"10.3390","volume":"21","author":[{"given":"Winston T.","family":"Stauffer","sequence":"first","affiliation":[{"name":"Department of Biology, San Diego State University Heart Institute, San Diego State University, San Diego, CA 92182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik A.","family":"Blackwood","sequence":"additional","affiliation":[{"name":"Department of Biology, San Diego State University Heart Institute, San Diego State University, San Diego, CA 92182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalid","family":"Azizi","sequence":"additional","affiliation":[{"name":"Department of Biology, San Diego State University Heart Institute, San Diego State University, San Diego, CA 92182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randal J.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"},{"name":"Department of Pharmacology, University of California, San Diego, La Jolla, CA 92161, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher C.","family":"Glembotski","sequence":"additional","affiliation":[{"name":"Department of Biology, San Diego State University Heart Institute, San Diego State University, San Diego, CA 92182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1161\/CIRCRESAHA.115.307778","article-title":"Revisiting Cardiac Cellular Composition","volume":"118","author":"Pinto","year":"2016","journal-title":"Circ. 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