Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF β1/Smad3 and NF-κB signaling pathways  

作　　者：Liu Shi Li Zhou Ming Han Yu Zhang Yang Zhang Xiao-Xue Yuan Hong-Ping Lu Yun Wang Xue-Liang Yang Chen Liu Jun Wang Pu Liang Shun-Ai Liu Xiao-Jing Liu Jun Cheng Shu-Mei Lin 

机构地区：[1]Department of Infectious Disease Medicine,The First Hospital Affiliated to Xi’an Jiaotong University,Xi’an 710061,Shaanxi Province,China [2]China-Japan Friendship Hospital,Department of Infectious Disease China-Japan Friendship Hospital,Beijing 100029,China [3]Institute of Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China [4]The Division of Liver Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China [5]Institute of Liver Diseases,Beijing Pan-Asia Tongze Institute of Biomedicine Co.,Ltd,Beijing 100015,China [6]Department of Rehabilitation Medicine,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,Shaanxi Province,China [7]Beijing Key Laboratory of Emerging Infectious Diseases,Peking University Ditan Teaching Hospital,Beijing 100015,China

出　　处：《World Journal of Gastroenterology》2023年第18期2798-2817,共20页世界胃肠病学杂志（英文版）

基　　金：the National Key Research and Development Program of China,No.2017YFC0908104;National Science and Technology Projects,No.2017ZX10203201,No.2017ZX10201201,and No.2017ZX10202202.

摘　　要：BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by

关 键 词：Nonstructural protein 3-transactivated protein 1 CALCITRIOL Liver fibrosis Hepatic stellate cells Mouse model TGFβ1/Smad3 NF-κB Signaling pathway 

分 类 号：R512.63[医药卫生—内科学]