{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:41:13Z","timestamp":1791232873091,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3196,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>JunD is implicated in the regulation of hepatic stellate cell (HSC) activation and liver fibrosis via its transcriptional regulation of the tissue inhibitor of metalloproteinases-1 (TIMP-1) gene. In the present study we found<\/jats:bold>\n                                 <jats:bold>\n                                    in vivo\n                                 <\/jats:bold>\n                                 <jats:bold>evidence of a role for JunD in fibrogenesis. Expression of JunD was demonstrated in alpha-SMA-positive activated HSCs of fibrotic rodents and human livers. The<\/jats:bold>\n                                 <jats:bold>\n                                    junD\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice were protected from carbon tetrachloride\u2013induced fibrosis. The livers of injured<\/jats:bold>\n                                 <jats:bold>\n                                    junD\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice displayed significantly reduced formation of fibrotic crosslinked collagen and a smaller number of alpha-SMA-positive HSCs compared with those of wild-type (wt) mice. Hepatic TIMP-1 mRNA expression in injured<\/jats:bold>\n                                 <jats:bold>\n                                    junD\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice was 78% lower and in culture activated<\/jats:bold>\n                                 <jats:bold>\n                                    junD\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 HSCs was 50%-80% lower than that in wt mice. In examining the signal transduction mechanisms that regulate JunD-dependent TIMP-1 expression, we found a role for phosphorylation of the Ser100 residue of JunD but ruled out JNK as a mediator of this event, suggesting ERK1\/2 is utilized.<\/jats:bold>\n                                 <jats:bold>\n                                    In conclusion\n                                 <\/jats:bold>\n                                 <jats:bold>, a signaling pathway for the development of fibrosis involves the regulation of TIMP-1 expression by phosphorylated JunD.<\/jats:bold>\n                                 <jats:bold>\n                                    Supplementary material for this article can be found on the HEPATOLOGY website\n                                 <\/jats:bold> (http:\/\/interscience.wiley.com\/jpages\/0270-9139\/suppmat\/index.html).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.21436","type":"journal-article","created":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T21:10:47Z","timestamp":1164748247000},"page":"1432-1440","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":44,"title":["JunD is a profibrogenic transcription factor regulated by Jun N-terminal kinase-independent phosphorylation"],"prefix":"10.1097","volume":"44","author":[{"given":"David E.","family":"Smart","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Oakley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"Weitzman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Yaniv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Millward-Sadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek A.","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-14-20241201","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1074\/jbc.275.4.2247","article-title":"Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury.","volume":"275","author":"Friedman","year":"2000","journal-title":"J Biol Chem"},{"key":"R2-14-20241201","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1055\/s-2001-17552","article-title":"Extracellular matrix degradation and the role of hepatic stellate cells.","volume":"21","author":"Benyon","year":"2001","journal-title":"Semin Liver Dis"},{"key":"R3-14-20241201","doi-asserted-by":"crossref","first-page":"11069","DOI":"10.1074\/jbc.M111490200","article-title":"Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase1 is mediated via effects on matrix metalloproteinase inhibition: implications for reversibility of liver fibrosis.","volume":"277","author":"Murphy","year":"2002","journal-title":"J Biol Chem"},{"key":"R4-14-20241201","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1002\/hep.510290333","article-title":"Control of the tissue inhibitor of metalloproteinases1 promoter in cultureactivated rat hepatic stellate cells: regulation by activator protein1 DNA binding proteins.","volume":"29","author":"Bahr","year":"1999","journal-title":"HEPATOLOGY"},{"key":"R5-14-20241201","doi-asserted-by":"crossref","first-page":"6657","DOI":"10.1074\/jbc.275.9.6657","article-title":", Samra S., Arthur MJP, Wright MC, McAuley M, Beri R, et al. 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