{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:44:05Z","timestamp":1790721845775,"version":"4.1.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":396,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"NIH","award":["DK076735"],"award-info":[{"award-number":["DK076735"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>\n                    <jats:bold>Abstract<\/jats:bold>\n                  <\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of Pdgfrb (Pdgfrb-Cre) inactivates loxP-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding \u03b1\n                      <jats:sub>V<\/jats:sub>\n                      integrin subunit because various \u03b1\n                      <jats:sub>V<\/jats:sub>\n                      -containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride-induced hepatic fibrosis, whereas global loss of \u03b23, \u03b25 or \u03b26 integrin or conditional loss of \u03b28 integrins in HSCs did not. We also found that Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of the \u03b1V integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of \u03b1\n                      <jats:sub>V<\/jats:sub>\n                      -containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all \u03b1\n                      <jats:sub>V<\/jats:sub>\n                      integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.27155","type":"journal-article","created":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T11:08:43Z","timestamp":1396436923000},"page":"756-758","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Integrins, myofibroblasts, and organ fibrosis"],"prefix":"10.1097","volume":"60","author":[{"given":"Michel","family":"Fausther","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan 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tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology.","volume":"4","author":"Mederacke","year":"2013","journal-title":"Nat Commun"},{"key":"R11-34-20250207","doi-asserted-by":"crossref","first-page":"10171028","DOI":"10.1002\/pmic.200900257","article-title":"Distinct proteomic features of two fibrogenic liver cell populations: hepatic stellate cells and portal myofibroblasts.","volume":"10","author":"Bosselut","year":"2010","journal-title":"Proteomics"},{"key":"R12-34-20250207","doi-asserted-by":"crossref","first-page":"225230","DOI":"10.1007\/s40139-013-0020-0","article-title":"Contribution of myofibroblasts of different origins to liver fibrosis.","volume":"1","author":"Fausther","year":"2013","journal-title":"Curr Pathobiol Rep"},{"key":"R14-34-20250207","doi-asserted-by":"crossref","first-page":"11511159","DOI":"10.1002\/hep.20427","article-title":"A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic 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