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Liver sinusoidal endothelial cells (LSECs) predominantly compose hepatic vascular niches. Endothelial cell (EC)\u2010expressing sphingosine 1\u2010phosphate receptor 2 (S1pr2) plays an essential role in the regulation of vascular functions. Nevertheless, it remains unknown whether liver LSEC\u2010S1pr2 might modulate pathological liver fibrosis. In this study, liver fibrosis was induced by hepatotoxin carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ). The expression of S1pr2 is significantly downregulated in liver sinusoidal endothelial cells after CCl\n                    <jats:sub>4<\/jats:sub>\n                    treatment. The loss of S1pr2 in LSECs significantly alleviated liver fibrosis after chronic insult, whereas the overexpression of S1pr2 in LSECs accentuated liver fibrogenesis. In vivo experiments further revealed that the deficiency of S1pr2 in LSECs dampened hepatic stellate cell (HSC) activation, while overexpression of S1pr2 in LSECs enhanced HSC activation with more extracellular matrix component production. Mechanistically, LSEC\u2010S1pr2 activates the YAP signaling pathway to potentiate the transactivation of TGF\u2010\u03b2, which acts on HSCs in a paracrine manner, and thus aggravated liver fibrosis. Taken together, our results uncover a novel pathological mechanism of liver fibrosis in which LSEC\u2010S1pr2 plays an important role in modulating the development of liver fibrosis, providing a future novel therapy target against liver fibrogenesis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202201954r","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T10:56:30Z","timestamp":1681210590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Liver sinusoidal endothelial S1pr2 regulates experimental liver fibrosis through\n                    <scp>YAP<\/scp>\n                    \/\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2 signaling pathway"],"prefix":"10.1096","volume":"37","author":[{"given":"Yang","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital Sichuan University  610041 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