{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:43:12Z","timestamp":1786977792300,"version":"build-2736575974"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1034,"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":[[2012,11]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>RNA-binding proteins (RBPs) play a major role in the control of messenger RNA (mRNA) turnover and translation rates. We examined the role of the RBP, human antigen R (HuR), during cholestatic liver injury and hepatic stellate cell (HSC) activation.<\/jats:bold>\n                      <jats:bold>HuR<\/jats:bold>\n                      <jats:bold>silencing attenuated fibrosis development<\/jats:bold>\n                      <jats:bold>in vivo<\/jats:bold>\n                      <jats:bold>after BDL, reducing liver damage, oxidative stress, inflammation, and collagen and alpha smooth muscle actin (\u03b1-SMA) expression. HuR expression increased in activated HSCs from bile duct ligation mice and during HSC activation<\/jats:bold>\n                      <jats:bold>in vitro<\/jats:bold>\n                      <jats:bold>, and<\/jats:bold>\n                      <jats:bold>HuR<\/jats:bold>\n                      <jats:bold>silencing markedly reduced HSC activation. HuR regulated platelet-derived growth factor (PDGF)-induced proliferation and migration and controlled the expression of several mRNAs involved in these processes (e.g.,<\/jats:bold>\n                      <jats:bold>Actin<\/jats:bold>\n                      <jats:bold>, matrix metalloproteinase 9, and<\/jats:bold>\n                      <jats:bold>cyclin D1<\/jats:bold>\n                      <jats:bold>and<\/jats:bold>\n                      <jats:bold>B1<\/jats:bold>\n                      <jats:bold>). These functions of HuR were linked to its abundance and cytoplasmic localization, controlled by PDGF, by extracellular signal-regulated kinases (ERK) and phosphatidylinositol 3-kinase activation as well as ERK\/LKB1 (liver kinase B1) activation, respectively. More important, we identified the tumor suppressor, LKB1, as a novel downstream target of PDGF-induced ERK activation in HSCs. HuR also controlled transforming growth factor beta (TGF-\u03b2)-induced profibrogenic actions by regulating the expression of<\/jats:bold>\n                      <jats:bold>TGF<\/jats:bold>\n                      <jats:bold>-\u03b2, \u03b1<\/jats:bold>\n                      -\n                      <jats:bold>SMA<\/jats:bold>\n                      <jats:bold>, and<\/jats:bold>\n                      <jats:bold>p21<\/jats:bold>\n                      <jats:bold>. This was likely the result of an increased cytoplasmic localization of HuR, controlled by TGF-\u03b2-induced p38 mitogen-activated protein kinase activation. Finally, we found that HuR and LKB1 (Ser428) levels were highly expressed in activated HSCs in human cirrhotic samples.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion :<\/jats:title>\n                    <jats:p>\n                      <jats:bold>Our results show that HuR is important for the pathogenesis of liver fibrosis development in the cholestatic injury model, for HSC activation, and for the response of activated HSC to PDGF and TGF-\u03b2.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.25828","type":"journal-article","created":{"date-parts":[[2012,5,10]],"date-time":"2012-05-10T07:51:52Z","timestamp":1336636312000},"page":"1870-1882","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":77,"title":["Human antigen R contributes to hepatic stellate cell activation and liver fibrosis"],"prefix":"10.1097","volume":"56","author":[{"given":"Ashwin","family":"Woodhoo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Iruarrizaga-Lejarreta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiara","family":"Beraza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan 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C","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M","family":"Mato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Varela-Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda L","family":"Mart\u00ednez-Chantar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"issue":"Suppl 3","key":"R1-31-20241202","first-page":"S79S83","article-title":"Transcriptional regulation of stellate cell activation.","volume":"21","author":"Friedman","year":"2006","journal-title":"J Gastroenterol Hepatol"},{"key":"R2-31-20241202","doi-asserted-by":"crossref","first-page":"8492","DOI":"10.1002\/hep.1840100117","article-title":"In situ hybridization for procollagen types I, III and IV mRNA in normal and fibrotic rat liver: 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