{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:55:45Z","timestamp":1790150145814,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,6,21]],"date-time":"2012-06-21T00:00:00Z","timestamp":1340236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human hepatic stellate cells (HHSCs) proliferation and migration play a key role in the pathogenesis of liver inflammation and fibrogenesis. Low density lipoprotein receptor\u2010related protein (LRP1) is an endocytic receptor involved in intracellular signal transduction. The aim of this work was to analyse the role of low density lipoprotein receptor\u2010related protein (LRP1) in HHSCs proliferation and migration and the mechanisms involved. Human LRP1 deficient\u2010HHSCs were generated by nucleofecting the line HHSCs with siRNA anti\u2010LRP1. HHSCs DNA synthesis was measured by [<jats:sup>3<\/jats:sup>H]\u2010thymidine incorporation and cell cycle progression by flow cytometry after annexin V and iodure propidium staining. Cell migration was assessed using a wound repair model system. LRP1 expression and extracellular matrix\u2010regulated kinase (ERK1,2) phosphorylation were analysed by Western blot analysis. Transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) extracellular levels were analysed by ELISA. siRNA\u2010antiLRP1 treatment almost completely inhibited LRP1 mRNA and protein expression. LRP1 deficient HHSCs showed higher proliferative response (172\u2009\u00b1\u200919 vs. 93\u2009\u00b1\u20098 [<jats:sup>3<\/jats:sup>H]\u2010thymidine incorporation; 78.68% vs. 82.69% in G0\/G1, 21.32% vs. 17.30% in G2\/S) and higher migration rates than control HHSCs. LRP1 deficient cells showed higher levels of phosphorylated ERK1,2. TGF\u2010\u03b2 extracellular levels were threefold higher in LRP1\u2010deficient than in control HHSCs cells. These results demonstrate that LRP1 regulates HHSCs proliferation and migration through modulation of ERK1,2 phosphorylation and TGF\u2010\u03b2 extracellular levels. These results suggest that HHSCs\u2010LRP1 may play a key role in the modulation of factors determining hepatic fibrosis. J. Cell. Physiol. 227: 3528\u20133533, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.24080","type":"journal-article","created":{"date-parts":[[2012,3,6]],"date-time":"2012-03-06T00:08:31Z","timestamp":1330992511000},"page":"3528-3533","source":"Crossref","is-referenced-by-count":15,"title":["Low density lipoprotein receptor\u2010related protein 1 modulates the proliferation and migration of human hepatic stellate 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