{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:55:04Z","timestamp":1792788904029,"version":"4.5.0"},"reference-count":52,"publisher":"American Physiological Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:p>\n                    Fibrosis is a common pathological sequela of tissue injury or inflammation, and is a major cause of organ failure. Subsets of fibroblasts contribute to tissue fibrosis in multiple ways, including generating contractile force to activate integrin-bound, latent TGF\u03b2 and secreting excess amounts of collagens and other extracellular matrix proteins (ECM) that make up pathologic scar. However, the precise fibroblast subsets that drive fibrosis have been poorly understood. In the absence of well-characterized markers, \u03b1-smooth muscle actin (\u03b1SMA) is often used to identify pathologic fibroblasts, and some authors have equated \u03b1SMA\n                    <jats:sup>+<\/jats:sup>\n                    cells with contractile myofibroblasts and proposed that these cells are the major source of ECM. Here, we investigated how well \u03b1SMA expression describes fibroblast subsets responsible for TGF\u03b2 activation and collagen production in three commonly used models of organ fibrosis that we previously reported could be inhibited by loss of \u03b1v integrins on all fibroblasts (using PDGFR\u03b2-Cre). Interestingly, \u03b1SMA-directed deletion of \u03b1v integrins protected mice from CCl4-induced hepatic fibrosis, but not bleomycin-induced pulmonary or unilateral ureteral obstruction\u2013induced renal fibrosis. Using Col-EGFP\/\u03b1SMA-RFP dual reporter mice, we found that only a minority of collagen-producing cells coexpress \u03b1SMA in the fibrotic lung and kidney. Notably, Col-EGFP\n                    <jats:sup>+<\/jats:sup>\n                    \u03b1SMA-RFP\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells isolated from the fibrotic lung and kidney were equally capable of activating TGF\u03b2 as were Col-EGFP\n                    <jats:sup>+<\/jats:sup>\n                    \u03b1SMA-RFP\n                    <jats:sup>+<\/jats:sup>\n                    cells from the same organ, and this TGF\u03b2 activation was blocked by a TGF\u03b2-blocking antibody and an inhibitor of nonmuscle myosin, respectively. Taken together, our results suggest that \u03b1SMA is an inconsistent marker of contractile and collagen-producing fibroblasts in murine experimental models of organ fibrosis.\n                  <\/jats:p>","DOI":"10.1152\/ajplung.00350.2015","type":"journal-article","created":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T22:49:09Z","timestamp":1457131749000},"page":"L824-L836","source":"Crossref","is-referenced-by-count":195,"title":["\u03b1-Smooth muscle actin is an inconsistent marker of fibroblasts responsible for force-dependent TGF\u03b2 activation or collagen production across multiple models of organ fibrosis"],"prefix":"10.1152","volume":"310","author":[{"given":"Kai-Hui","family":"Sun","sequence":"first","affiliation":[{"name":"Lung Biology Center, Department of Medicine, University of California, San Francisco; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongen","family":"Chang","sequence":"additional","affiliation":[{"name":"Lung Biology Center, Department of Medicine, University of California, San Francisco; and"},{"name":"Division of Nephrology, Department of Medicine, University of California, Irvine, Orange, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilgun I.","family":"Reed","sequence":"additional","affiliation":[{"name":"Lung Biology Center, Department of Medicine, University of California, San Francisco; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Sheppard","sequence":"additional","affiliation":[{"name":"Lung Biology Center, Department of Medicine, University of California, San Francisco; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1994.1042"},{"key":"B2","first-page":"473","volume":"60","author":"Adler KB","year":"1989","journal-title":"Lab Invest"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.035246"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200312172"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)03280-X"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.11.7708"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.041306"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-17558"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60387"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72267"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1513\/pats.201203-023AW"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.10.034"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.24.8681"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.01.020"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/stem.150190"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2006.tb00292.x"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060158"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3282"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.10.005"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/thx.11.2.77"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.02.004"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2174\/138920111798808419"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400062111"},{"key":"B24","first-page":"1257","volume":"138","author":"Kuhn C","year":"1991","journal-title":"AM J Pathol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707421104"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010819716023"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00173"},{"key":"B28","first-page":"885","volume":"29","author":"Liebow AA","year":"1953","journal-title":"Am J Pathol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20427"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2009.276"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00082"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200109100"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.9.9.2627"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80545-0"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005017"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152238499"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1378\/chest.122.6_suppl.286S"},{"key":"B39","volume":"7","author":"Reed NI","year":"2015","journal-title":"Scie Transl Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2741\/reeves"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400029200"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1117988108"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1136\/thx.22.4.291"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/jhbp.245"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nature10152"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-5-11"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1997.2026"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21849"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119663"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1550061"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200704042"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50067"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00350.2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T21:54:25Z","timestamp":1567979665000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00350.2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,1]]},"references-count":52,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,5,1]]}},"alternative-id":["10.1152\/ajplung.00350.2015"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00350.2015","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,1]]}}}