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Peroxisome proliferator-activated receptor beta\/delta\n                      <jats:bold>(<\/jats:bold>\n                      PPAR\u03b2\/\u03b4) is highly expressed in these cells, but its function in liver repair remains incompletely understood. This study investigated whether activation of PPAR\u03b2\/\u03b4 with the ligand GW501516 influenced the fibrotic response to injury from chronic carbon tetrachloride (CCl\n                      <jats:sub>4<\/jats:sub>\n                      ) treatment in mice. Wild type and PPAR\u03b2\/\u03b4-null mice were treated with CCl\n                      <jats:sub>4<\/jats:sub>\n                      alone or CCl\n                      <jats:sub>4<\/jats:sub>\n                      co-administered with GW501516. To unveil mechanisms underlying the PPAR\u03b2\/\u03b4-dependent effects, we analyzed the proliferative response of human LX-2 HSCs to GW501516 in the presence or absence of PPAR\u03b2\/\u03b4.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that GW501516 treatment enhanced the fibrotic response. Compared to the other experimental groups, CCl\n                      <jats:sub>4<\/jats:sub>\n                      \/GW501516-treated wild type mice exhibited increased expression of various profibrotic and pro-inflammatory genes, such as those involved in extracellular matrix deposition and macrophage recruitment. Importantly, compared to healthy liver, hepatic fibrotic tissues from alcoholic patients showed increased expression of several PPAR target genes, including phosphoinositide-dependent kinase-1, transforming growth factor beta-1, and monocyte chemoattractant protein-1. GW501516 stimulated HSC proliferation that caused enhanced fibrotic and inflammatory responses, by increasing the phosphorylation of p38 and c-Jun N-terminal kinases through the phosphoinositide-3 kinase\/protein kinase-C alpha\/beta mixed lineage kinase-3 pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study clarified the mechanism underlying GW501516-dependent promotion of hepatic repair by stimulating proliferation of HSCs\n                      <jats:italic>via<\/jats:italic>\n                      the p38 and JNK MAPK pathways.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/2045-3701-2-34","type":"journal-article","created":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T13:05:32Z","timestamp":1349874332000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["GW501516-activated PPAR\u03b2\/\u03b4 promotes liver fibrosis via p38-JNK MAPK-induced hepatic stellate cell proliferation"],"prefix":"10.1186","volume":"2","author":[{"given":"Radina","family":"Kostadinova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Montagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwan","family":"Gouranton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Fleury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Guillou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dombrowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Desreumaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Wahli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,10,10]]},"reference":[{"key":"80_CR1","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1007\/s10495-005-1055-4","volume":"10","author":"AM Elsharkawy","year":"2005","unstructured":"Elsharkawy AM, Oakley F, Mann DA: The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis. 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