S-nitrosylation of EMMPRIN influences the migration of HSCs and MMP activity in liver fibrosis  

作　　者：Xinyan Zhu Zihui Tang Wei Li Xiaojuan Li Yasuko Iwakiri Fei Liu 

机构地区：[1]Department of Gastroenterology,Shanghai East Hospital,School of Medicine,Tongji University,Shanghai 200092,China [2]Section of Digestive Diseases,Department of Internal Medicine,Yale School of Medicine,New Haven,CT 06520,USA [3]Department of Gastroenterology,Pinghu Second People’s Hospital,Jiaxing 314201,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第10期1640-1649,共10页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Natural Science Foundation of China(No.81970538);the Medical discipline Construction Project of Pudong Health Committee of Shanghai(No.PWYgf 2021-02);the Key Disciplines Group Construction Project of Shanghai Pudong New Area Health Commission(No.PWZxq2022-06);the Science and Technology Development Fund of Pudong New Area(No.PKJ2022-Y19).

摘　　要：The mechanism of extracellular matrix metalloproteinase inducer(EMMPRIN)in the regulation of liver fibrosis has not been clarified.This study aims to investigate the role of EMMPRIN S-nitrosylation(SNO)in the regulation of hepatic stellate cell(HSC)migration and matrix metalloproteinase(MMP)activities in liver fibrosis.The results from the tissue microarrays and rat/mouse liver tissues suggest that EMMPRIN mRNA and protein levels in the fibrotic livers are lower than those in the corresponding normal control livers,but higher SNO level of EMMPRIN in fibrotic liver area was shown by immunohistochemistry,immunofluorescence staining,and biotin-switch assay conversely in vivo.Primary EMMPRIN comes from hepatocytes and liver sinus epithelial cells(LSECs)rather than quiescent HSCs.To mimic the uptake of extrinsic EMMPRIN,supernatants from mouse primary hepatocytes/293 cells transfected with EMMPRIN wild-type plasmids(WT)and EMMPRIN SNO site(cysteine 87)mutation plasmids(MUT)were collected and added to JS-1/LX2 cell medium.The MUT EMMPRIN diminishes SNO successfully,enhances the activities of MMP2 and MMP9,and subsequently increases HSC migration.In conclusion,SNO of EMMPRIN influences HSC migration and MMP activities in liver fibrosis.This finding may shed light on the possible regulatory mechanism of MMPs in ECM accumulation in liver fibrosis.

关 键 词：liver fibrosis extracellular matrix metalloproteinase inducer(EMMPRIN) S-nitrosylation(SNO) matrix metalloproteinases(MMPs) cell migration 

分 类 号：R575[医药卫生—消化系统]