Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1.
Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1.
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DOI：
10.1371/journal.pone.0261789
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Green RM
中科院分区：
文献类型：
--
作者：
Liu X;Taylor SA;Gromer KD;Zhang D;Hubchak SC;LeCuyer BE;Iwawaki T;Shi Z;Rockey DC;Green RM
非酒精性脂肪性肝病（NAFLD）是美国最常见的肝病原因之一，可以进展为肝硬化，终末期肝病和需要肝移植。NAFLD的治疗方法有限，部分原因是对疾病发病机制的不完全理解，这涉及肝脏中的不同细胞群。内质网应激及其适应性未折叠蛋白反应（UPR）信号通路参与了单纯性脂肪肝向非酒精性脂肪性肝炎（NASH）的进展。我们先前已经表明，在肝脏中缺乏UPR蛋白X盒结合蛋白1（XBP1）的小鼠在NAFLD的高脂糖（HFS）饮食模型中表现出增强的肝损伤和纤维化。在这项研究中，为了更好地了解肝脏XBP1在NAFLD病理生物学中的作用，我们给肝细胞XBP1缺陷小鼠喂食HFS饮食或食物，并研究了肝细胞，肝星状细胞和免疫细胞中的UPR和其他细胞信号传导途径。我们证明，肝细胞中XBP1的丢失增加了炎症通路的表达，改变了肝细胞中UPR信号的表达，并与HFS喂养后增强的肝星状细胞活化相关。我们相信，更好地理解NASH发病机制中的肝细胞特异性信号传导可能使我们能够确定新的治疗靶点。
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver diseases in the United States and can progress to cirrhosis, end-stage liver disease and need for liver transplantation. There are limited therapies for NAFLD, in part, due to incomplete understanding of the disease pathogenesis, which involves different cell populations in the liver. Endoplasmic reticulum stress and its adaptative unfolded protein response (UPR) signaling pathway have been implicated in the progression from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). We have previously shown that mice lacking the UPR protein X-box binding protein 1 (XBP1) in the liver demonstrated enhanced liver injury and fibrosis in a high fat sugar (HFS) dietary model of NAFLD. In this study, to better understand the role of liver XBP1 in the pathobiology of NAFLD, we fed hepatocyte XBP1 deficient mice a HFS diet or chow and investigated UPR and other cell signaling pathways in hepatocytes, hepatic stellate cells and immune cells. We demonstrate that loss of XBP1 in hepatocytes increased inflammatory pathway expression and altered expression of the UPR signaling in hepatocytes and was associated with enhanced hepatic stellate cell activation after HFS feeding. We believe that a better understanding of liver cell-specific signaling in the pathogenesis of NASH may allow us to identify new therapeutic targets.
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DOI：
10.1002/hep.30150
发表时间：
2019-01
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Sato K;Marzioni M;Meng F;Francis H;Glaser S;Alpini G
通讯作者：
Alpini G
影响因子：
6.5
作者：
Liu, Xiaoying;Henkel, Anne S.;Green, Richard M.
通讯作者：
Green, Richard M.
影响因子：
56.9
作者：
Lee, Ann-Hwee;Scapa, Erez F.;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.
影响因子：
13.5
作者：
Gadd, Victoria L.;Skoien, Richard;Clouston, Andrew D.
通讯作者：
Clouston, Andrew D.
DOI：
10.1152/ajpgi.00132.2015
发表时间：
2015-12-15
影响因子：
4.5
作者：
Liu, Xiaoying;Henkel, Anne S.;Green, Richard M.
通讯作者：
Green, Richard M.