{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:56:33Z","timestamp":1793141793626,"version":"4.5.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,6,12]]},"abstract":"<jats:p>\n                    Myofibroblasts produce the fibrous scar in hepatic fibrosis. In the carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) model of liver fibrosis, quiescent hepatic stellate cells (HSC) are activated to become myofibroblasts. When the underlying etiological agent is removed, clinical and experimental fibrosis undergoes a remarkable regression with complete disappearance of these myofibroblasts. Although some myofibroblasts apoptose, it is unknown whether other myofibroblasts may revert to an inactive phenotype during regression of fibrosis. We elucidated the fate of HSCs\/myofibroblasts during recovery from CCl\n                    <jats:sub>4<\/jats:sub>\n                    - and alcohol-induced liver fibrosis using Cre-LoxP\u2013based genetic labeling of myofibroblasts. Here we demonstrate that half of the myofibroblasts escape apoptosis during regression of liver fibrosis, down-regulate fibrogenic genes, and acquire a phenotype similar to, but distinct from, quiescent HSCs in their ability to more rapidly reactivate into myofibroblasts in response to fibrogenic stimuli and strongly contribute to liver fibrosis. Inactivation of HSCs was associated with up-regulation of the anti-apoptotic genes Hspa1a\/b, which participate in the survival of HSCs in culture and in vivo.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1201840109","type":"journal-article","created":{"date-parts":[[2012,5,8]],"date-time":"2012-05-08T03:17:40Z","timestamp":1336447060000},"page":"9448-9453","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":767,"title":["Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis"],"prefix":"10.1073","volume":"109","author":[{"given":"Tatiana","family":"Kisseleva","sequence":"first","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YongHan","family":"Paik","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-720, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Scholten","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Department of Medicine III, University Hospital Aachen, Aachen 52074, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Benner","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Iwaisako","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Moore-Morris","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of California, San Diego, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia M.","family":"Evans","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of California, San Diego, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Dillmann","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K.","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,5,7]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1018"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.049"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.24.8681"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410078200"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040104"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006721"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1663"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118304"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209175200"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.00980.x"},{"key":"e_1_3_2_12_2","first-page":"219","article-title":"Multiparameter flow cytometry of fluorescent protein reporters","volume":"263","author":"Hawley TS","year":"2004","unstructured":"TS Hawley, DJ Herbert, SS Eaker, RG Hawley, Multiparameter flow cytometry of fluorescent protein reporters. 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