title: Liver X receptor α is essential for the capillarization of liver sinusoidal endothelial cells in liver injury.
abstract: Liver X receptors (LXRs) play essential roles in lipogenesis, anti-inflammatory action and hepatic stellate cells (HSCs) activation in the liver. However, the effects of LXRs on the capillarization of liver sinusoidal endothelial cells (LSECs) in liver fibrosis remain undetermined. Here, we demonstrated that LXRα plays an important role in LSECs capillarization in a manner that involved Hedgehog (Hh) signaling. We found that LXRα expression in LSECs was increased in the carbon tetrachloride (CCl4)-induced fibrosis model. LXRα deletion markedly exacerbated CCl4-induced lesions assessed by histopathology, as well as inflammation and collagen deposition. Furthermore, capillarization of the sinusoids was aggravated in CCl4 -treated LXRα-deficient mice, as evidenced by increased CD34 expression, the formation of continuous basement membranes and aggravation of the loss of fenestrae. In vitro, LXR agonist could maintain freshly isolated LSECs differentiation on day 3. Furthermore, LXRα deletion led to increased expression of Hedgehog (Hh)-regulated gene in LSECs in the injured liver. Conversely, the LXR agonist could inhibit the Hh pathway in cultured LSECs. These responses indicated that LXRα suppressed the process of LSECs capillarization by repressing Hh signaling. Overall, our findings suggest that LXRα, by restoring the differentiation of LSECs, may be critical for the regression of liver fibrosis.
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, PR China.|Department of anatomy, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, PR China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, PR China.
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism* / Q000473:pathology; D002252:Carbon Tetrachloride Poisoning / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000098:blood supply* / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D000071518:Liver X Receptors