{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:04:50Z","timestamp":1791029090906,"version":"4.1.0"},"reference-count":50,"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>Liver fibrosis, a common scarring response to chronic liver injury, is a precursor to cirrhosis and liver cancer. Here, we identified signal transducer and activator of transcription 1 (STAT1) as an important negative regulator in liver fibrosis. Our findings show that disruption of the STAT1 gene accelerated liver fibrosis and hepatic stellate cell (HSC) proliferation in an<\/jats:bold>\n                      <jats:bold>in vivo<\/jats:bold>\n                      <jats:bold>model of carbon tetrachloride (CCl4)-induced liver fibrosis.<\/jats:bold>\n                      <jats:bold>In vitro<\/jats:bold>\n                      <jats:bold>treatment with IFN-\u03b3 inhibited proliferation and activation of wild-type HSCs, but not STAT1\u2212\/\u2212 HSCs. Moreover, compared to wild-type cells, cellular proliferation stimulated by serum or platelet-derived growth factor (PDGF) was enhanced and accelerated in STAT1\u2212\/\u2212 HSCs, which was partially mediated via elevated PDGF receptor \u03b2 expression on such cells. Polyinosinic-polycytidylic acid (poly I:C) or IFN-\u03b3 treatment inhibited liver fibrosis in wild-type mice but not in STAT1\u2212\/\u2212 mice. Induction of NK cell killing of activated HSCs by poly I:C was attenuated in STAT1\u2212\/\u2212 mice compared to wild-type mice, which was likely due to reduced NKG2D and TRAIL expression on STAT1\u2212\/\u2212 NK cells. Finally, activation of TGF-\u03b2\/Smad3 signaling pathway was accelerated, whereas induction of Smad7 was diminished in the liver of STAT1\u2212\/\u2212 mice after CCl4 administration compared to wild-type mice.<\/jats:bold>\n                      <jats:bold>In conclusion<\/jats:bold>\n                      <jats:bold>, activation of STAT1 attenuates liver fibrosis through inhibition of HSC proliferation, attenuation of TGF-\u03b2 signaling, and stimulation of NK cell killing of activated HSCs. STAT1 could be a new therapeutic target for treating liver fibrosis.<\/jats:bold>\n                      <jats:bold>Supplementary material for this article can be found on the HEPATOLOGY website<\/jats:bold>\n                      (http:\/\/interscience.wiley.com\/jpages\/0270-9139\/suppmat\/index.html).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.21419","type":"journal-article","created":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T16:11:13Z","timestamp":1164730273000},"page":"1441-1451","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":250,"title":["STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell 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