典型文献
Hepatic NCoR1 deletion exacerbates alcohol-induced liver injury in mice by promoting CCL2-mediated monocyte-derived macrophage infiltration
文献摘要：
Nuclear receptor corepressor 1(NCoR1)is a corepressor of the epigenetic regulation of gene transcription that has important functions in metabolism and inflammation,but little is known about its role in alcohol-associated liver disease(ALD).In this study,we developed mice with hepatocyte-specific NCoR1 knockout(NCoR1Hep-/-)using the albumin-Cre/LoxP system and investigated the role of NCoR1 in the pathogenesis of ALD and the underlying mechanisms.The traditional alcohol feeding model and NIAAA model of ALD were both established in wild-type and NCoR1Hep-/-mice.We showed that after ALD was established,NCoR1Hep-/-mice had worse liver injury but less steatosis than wild-type mice.We demonstrated that hepatocyte-specific loss of NCoR1 attenuated liver steatosis by promoting fatty acid oxidation by upregulating BMAL1(a circadian clock component that has been reported to promote peroxisome proliferator activated receptor alpha(PPARα)-mediated fattyβ-oxidation by upregulating de novo lipid synthesis).On the other hand,hepatocyte-specific loss of NCoR1 exacerbated alcohol-induced liver inflammation and oxidative stress by recruiting monocyte-derived macrophages via C-C motif chemokine ligand 2(CCL2).In the mouse hepatocyte line AML12,NCoR1 knockdown significantly increased ethanol-induced CCL2 release.These results suggest that hepatocyte NCoR1 plays distinct roles in controlling liver inflammation and steatosis,which provides new insights into the development of treatments for steatohepatitis induced by chronic alcohol consumption.
文献关键词：
中图分类号：
作者姓名：
Fan Yin;Miao-miao Wu;Xiao-li Wei;Rui-xue Ren;Meng-hua Liu;Chong-qing Chen;Liu Yang;Rui-qian Xie;Shan-yue Jiang;Xue-fu Wang;Hua Wang
作者机构：
School of Pharmacy,Anhui Medical University,Hefei 230032,China;Department of Oncology,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;Inflammation and Immune Mediated Diseases Laboratory of Anhui Province,Anhui Medical University,Hefei 230032,China
文献出处：
引用格式：
[1]Fan Yin;Miao-miao Wu;Xiao-li Wei;Rui-xue Ren;Meng-hua Liu;Chong-qing Chen;Liu Yang;Rui-qian Xie;Shan-yue Jiang;Xue-fu Wang;Hua Wang-.Hepatic NCoR1 deletion exacerbates alcohol-induced liver injury in mice by promoting CCL2-mediated monocyte-derived macrophage infiltration)[J].中国药理学报（英文版）,2022(09):2351-2361
A类：
NCoR1,corepressor,NCoR1Hep
B类：
Hepatic,deletion,exacerbates,alcohol,induced,liver,injury,mice,by,promoting,CCL2,mediated,monocyte,derived,infiltration,Nuclear,receptor,epigenetic,regulation,transcription,that,has,important,functions,metabolism,inflammation,but,little,known,about,its,associated,disease,ALD,In,this,study,developed,hepatocyte,specific,knockout,using,albumin,Cre,LoxP,system,investigated,pathogenesis,underlying,mechanisms,traditional,feeding,model,NIAAA,were,both,established,wild,type,We,showed,after,was,had,worse,less,steatosis,demonstrated,loss,attenuated,fatty,acid,oxidation,upregulating,BMAL1,circadian,clock,component,been,reported,promote,peroxisome,proliferator,activated,alpha,PPAR,novo,lipid,synthesis,On,other,hand,exacerbated,oxidative,stress,recruiting,macrophages,via,motif,chemokine,ligand,mouse,line,AML12,knockdown,significantly,increased,ethanol,release,These,results,suggest,plays,distinct,roles,controlling,which,provides,new,insights,into,development,treatments,steatohepatitis,chronic,consumption
AB值：
0.546052
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