Role of retinol ester specific lipid droplet in hepatic stellate cell activation

来源 :The 9th Asian Biophysics Association Symposium (ABA2015)(第九届 | 被引量 : 0次 | 上传用户:laoqiangshou
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Liver fibrosis is a frequent, life-threatening complication in modern life.Despite major achievements in the understanding of its pathogenesis, the reversible treatment is still limited.Many studies have explored activation of hepatic stellate cells (HSCs) as a key event in fibrogenesis.Quiescent HSCs store retinol ester and triacylglycerol (TAG) in cytoplasmic lipid droplets (LDs).Reduction of LDs is a characteristic feature of HSC activation, but the relationship between LDs and HSC activation still remains unclear.We focus on HSCs as a turning point to alleviate and even to reverse hepatic fibrosis.Since we have established a LD study system including isolation, proteomics, and lipidomics, we analyzed the neutral lipid core and the surface proteins of HSC LDs.Because of the insufficiency quantity of primary HSCs, we isolated LDs using LX-2 human immortalized HSCs.Of reporting the 286 LD-associated proteins in the proteome of HSCs, five major proteins, perilipin2 (ADRP), perilipin3 (Tip47), lanosterol synthase, Acyl-CoA synthetase long-chain acyl-CoA synthetase (ACSL), and hydroxysteroid (17-beta)dehydrogenase constituted about half of the total LD proteins.Interestingly, retinol, oleic acid (OA), and palmitic acid (PA) were not only involved the synthesis of different neutral lipids in the LDs but also altered LD surface protein composition, that in turn played roles in HSC activation.Our results highlight the role of LDs in inhibition of HSC activation.These findings provide some hints toward a therapeutic strategy for treatment of hepatic fibrosis.
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