Liver X Receptor Signaling Is a Determinant of Stellate Cell Activation and Susceptibility to Fibrotic Liver Disease

摘要: Background & Aims Liver X receptors (LXRs) are lipid-activated nuclear with important roles in cholesterol transport, lipogenesis, and anti-inflammatory signaling. Hepatic stellate cells activate during chronic liver injury mediate the fibrotic response. These also major repositories for lipids, but role of lipid metabolism cell activation remains unclear. We investigated LXR signaling susceptibility to disease. Methods Immortalized primary purified from mice were treated highly specific ligands. Carbon tetrachloride methionine/choline deficiency used as models. Reciprocal bone marrow transplants performed test importance hematopoietically derived Results ligands suppressed markers fibrosis mouse cells. Lxr αβ −/− produce increased levels inflammatory mediators, conditioned media increases fibrogenic program wild-type Furthermore, exhibit altered morphology expression genes, suggesting they primed activation. In vivo, have marked 2 Bone point function, rather than hematopoietic inflammation, basis phenotype. Conclusions results reveal an unexpected modulation hepatic function.