@article{996a73772c0f4b69bed9815621554c4c,
title = "The ER unfolded protein response effector, ATF6, reduces cardiac fibrosis and decreases activation of cardiac fibroblasts",
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.",
keywords = "ATF6, Cardiac fibroblast, Cardiac fibrosis, ER stress, Endoplasmic reticulum, Smad, TGFβ, UPR",
author = "Stauffer, {Winston T.} and Blackwood, {Erik A.} and Khalid Azizi and Kaufman, {Randal J.} and Glembotski, {Christopher C.}",
note = "Funding Information: Funding: This research was funded by the American Heart Association (17PRE33670796 E.A.B.) and the National Institutes of Health 1F31HL140850 (E.A.B.), R01HL135893, R01 HL141463, and R01 HL149931 (C.C.G.), 1R01CA198103‐03, 1R01DK113171‐01A1, and R01AG062190‐01 (R.J.K.), the San Diego State University (SDSU) Heart Institute (W.T.S., E.A.B., and C.C.G.), the Inamori Foundation (E.A.B.), and the ARCS{\textregistered} Foundation, Inc, San Diego Chapter (W.T.S. and E.A.B). Additionally, W.T.S. and E.A.B are Rees‐Stealy Research Foundation Phillips Gausewitz, M.D., Scholars of the SDSU Heart Institute. Funding Information: This research was funded by the American Heart Association (17PRE33670796 E.A.B.) and the National Institutes of Health 1F31HL140850 (E.A.B.), R01HL135893, R01 HL141463, and R01 HL149931 (C.C.G.), 1R01CA198103?03, 1R01DK113171?01A1, and R01AG062190?01 (R.J.K.), the San Diego State University (SDSU) Heart Institute (W.T.S., E.A.B., and C.C.G.), the Inamori Foundation (E.A.B.), and the ARCS? Foundation, Inc, San Diego Chapter (W.T.S. and E.A.B). Additionally, W.T.S. and E.A.B are Rees?Stealy Research Foundation Phillips Gausewitz, M.D., Scholars of the SDSU Heart Institute. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = feb,
day = "2",
doi = "10.3390/ijms21041373",
language = "English (US)",
volume = "21",
journal = "International Journal of Molecular Sciences",
issn = "1422-0067",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",
}