{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:50:48Z","timestamp":1783939848347,"version":"3.55.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>During liver injury, quiescent hepatic stellate cells (qHSCs) transdifferentiate into proliferative and fibrogenic activated myofibroblastic phenotype (activated hepatic stellate cell; aHSCs) expressing smooth muscle \u03b1\u2010actin (\u03b1SMA) and platelet\u2010derived growth factor beta receptor (PDGF\u03b2R). Their interactions with gut\u2010derived bacterial lipopolysaccharide (LPS) are implicated in hepatic fibrogenesis. However, LPS can also attenuate fibrogenic characteristics of aHSCs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We examined molecular mechanisms of antifibrogenic effects of LPS on aHSCs <jats:italic toggle=\"yes\">in vitro<\/jats:italic> and <jats:italic toggle=\"yes\">in vivo<\/jats:italic>. Culture\u2010activated rat HSCs were exposed to 0\u2010100\u00a0ng\/mL of LPS or its active component, diphosphoryl\u2010lipid A (DPLA), and parameters of fibrosis and inflammatory cytokines\/chemokines were determined by qRT\u2010PCR, western, and immunohistochemical analyses. <jats:italic toggle=\"yes\">In vivo<\/jats:italic>, HSCs were activated by repeated CCl<jats:sub>4<\/jats:sub> administration to rats every 3\u00a0days for 3 or 8\u00a0weeks, then challenged with LPS (5\u00a0mg\/kg; IP). HSCs were isolated 24\u00a0hours later, and fibrogenic\/inflammatory parameters were analyzed. LPS induced phenotypic changes in aHSCs (rounding, size reduction) and loss of proliferation. LPS down\u2010regulated expression of \u03b1SMA, PDGF\u03b2R, transforming growth factor beta receptor 1 (TGF\u03b2R1), collagen 1\u03b11 (Col1\u03b11), and fibronectin while up\u2010regulating tumor necrosis factor alpha, interleukin\u20106, and C\u2010X\u2010C motif chemokine ligand 1 expression. LPS did not increase peroxisome proliferation\u2010activated receptor gamma expression or lipid accumulation typical of qHSCs. DPLA elicited the same effects as LPS on aHSCs, indicating specificity, and monophosphoryl lipid A down\u2010regulated fibrogenic markers, but elicited very weak inflammatory response. LPS down\u2010regulated the expression of cMyb, a transcription factor for \u03b1SMA, and up\u2010regulated small mother against decapentaplegic (SMAD)7 and CCAAT\/enhancer\u2010binding protein (C\/EBP)\u03b4, the transcriptional inhibitors of Col1\u03b11 expression. <jats:italic toggle=\"yes\">In vivo<\/jats:italic> LPS treatment of aHSCs inhibited their proliferation, down\u2010regulated PDGF\u03b2R, \u03b1SMA, TGF\u03b2R1, Col1\u03b11, and cMyb expression, and increased expression of SMAD7, C\/EBP\u03b1, and C\/EBP\u03b4.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In conclusion, LPS induces a unique phenotype in aHSCs associated with down\u2010regulation of key fibrogenic mechanisms and thus may have an important role in limiting fibrosis.<\/jats:p>\n          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