{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:02:39Z","timestamp":1790881359508,"version":"4.1.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2005,6]]},"abstract":"<jats:p>\n                    Pulmonary fibrosis is a progressive life-threatening disease for which no effective therapy exists. Myofibroblasts are one of the key effector cells in pulmonary fibrosis and are the primary source of extracellular matrix production. Drugs that inhibit the differentiation of fibroblasts to myofibroblasts have potential as antifibrotic therapies. Peroxisome proliferator-activated receptor (PPAR)-\u03b3 is a transcription factor that upon ligation with PPAR\u03b3 agonists activates target genes containing PPAR response elements. PPAR\u03b3 agonists have anti-inflammatory activities and may have potential as antifibrotic agents. In this study, we examined the abilities of PPAR\u03b3 agonists to block two of the most important profibrotic activities of TGF-\u03b2 on pulmonary fibroblasts: myofibroblast differentiation and production of excess collagen. Both natural (15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    ) and synthetic (ciglitazone and rosiglitazone) PPAR\u03b3 agonists inhibited TGF-\u03b2-driven myofibroblast differentiation, as determined by \u03b1-smooth muscle actin-specific immunocytochemistry and Western blot analysis. PPAR\u03b3 agonists also potently attenuated TGF-\u03b2-driven type I collagen protein production. A dominant-negative PPAR\u03b3 partially reversed the inhibition of myofibroblast differentiation by 15d-PGJ\n                    <jats:sub>2<\/jats:sub>\n                    and rosiglitazone, but the irreversible PPAR\u03b3 antagonist GW-9662 did not, suggesting that the antifibrotic effects of the PPAR\u03b3 agonists are mediated through both PPAR\u03b3-dependent and independent mechanisms. Thus PPAR\u03b3 agonists have novel and potent antifibrotic effects in human lung fibroblasts and may have potential for therapy of fibrotic diseases in the lung and other tissues.\n                  <\/jats:p>","DOI":"10.1152\/ajplung.00383.2004","type":"journal-article","created":{"date-parts":[[2005,2,25]],"date-time":"2005-02-25T20:14:18Z","timestamp":1109362458000},"page":"L1146-L1153","source":"Crossref","is-referenced-by-count":266,"title":["PPAR\u03b3 agonists inhibit TGF-\u03b2 induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis"],"prefix":"10.1152","volume":"288","author":[{"given":"Heather A.","family":"Burgess","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis Eugene","family":"Daugherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Thatcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather F.","family":"Lakatos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise M.","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Redonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Phipps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia 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