HBV infection upregulates GP73 expression to promote liver fibrosis by enhancing ER stress via the Smad2 pathway

Roehlen N, Crouchet E, Baumert TF: Liver fibrosis: mechanistic concepts and therapeutic perspectives. Cells 2020;9(4).

Caligiuri A, Gentilini A, Pastore M, Gitto S, Marra F: Cellular and molecular mechanisms underlying liver fibrosis regression. Cells 2021;10(10).

Rizzo GEM, Cabibbo G, Craxì A: Hepatitis B virus-associated hepatocellular carcinoma. Viruses 2022;14(5).

Lee HW, Lee JS, Ahn SH: Hepatitis B virus cure: targets and future therapies. Int J Mol Sci 2020; 22(1).

Kladney RD, Cui X, Bulla GA, Brunt EM, Fimmel CJ. Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease. Hepatology. 2002;35(6):1431–40.

Article  PubMed  CAS  Google Scholar 

Liu MY, Huang L, Wu JF, Zhang HB, Ai WB, Zhang RT. Possible roles of Golgi protein-73 in liver diseases. Ann Hepatol. 2022;27(5): 100720.

Article  PubMed  CAS  Google Scholar 

Huang F, Guo J, Zhao N, Hou M, Gai X, Yang S, Cai P, Wang Y, Ma Q, Zhao Q, et al. PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1. J Transl Med. 2024;22(1):254.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Liu L, Huang Y, Fu Y, Rao J, Zeng F, Ji M, Xu X, Zhu J, Du W, Liu Z. Hepatitis B virus promotes hepatocellular carcinoma development by activating GP73 to repress the innate immune response. Infect Agent Cancer. 2022;17(1):52.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Choi YM, Lee SY, Kim BJ: Naturally occurring hepatitis B virus mutations leading to endoplasmic reticulum stress and their contribution to the progression of hepatocellular carcinoma. Int J Mol Sci 2019;20(3).

Li Z, Huang Z, Zhang H, Lu J, Wei Y, Yang Y, Bai L. IRE1-mTOR-PERK axis coordinates autophagy and ER stress-apoptosis induced by P2X7-mediated Ca(2+) influx in osteoarthritis. Front Cell Dev Biol. 2021;9: 695041.

Article  PubMed  PubMed Central  Google Scholar 

Sun S, Huan S, Li Z, Yao Y, Su Y, Xia S, Wang S, Xu X, Shao J, Zhang Z, et al. Curcumol alleviates liver fibrosis by inducing endoplasmic reticulum stress-mediated necroptosis of hepatic stellate cells through Sirt1/NICD pathway. PeerJ. 2022;10: e13376.

Article  PubMed  PubMed Central  Google Scholar 

Zhang Z, Leng XK, Zhai YY, Zhang X, Sun ZW, Xiao JY, Lu JF, Liu K, Xia B, Gao Q, et al. Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress. Nat Commun. 2024;15(1):1908.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Wu N, Jiang M, Liu H, Chu Y, Wang D, Cao J, Wang Z, Xie X, Han Y, Xu B. LINC00941 promotes CRC metastasis through preventing SMAD4 protein degradation and activating the TGF-β/SMAD2/3 signaling pathway. Cell Death Differ. 2021;28(1):219–32.

Article  PubMed  CAS  Google Scholar 

Wang AH, Ma HY, Yi YL, Zhu SJ, Yu ZW, Zhu J, Mei S, Bahetibike S, Lu YQ, Huang LT, et al. Oleanolic acid derivative alleviates cardiac fibrosis through inhibiting PTP1B activity and regulating AMPK/TGF-β/Smads pathway. Eur J Pharmacol. 2023;960: 176116.

Article  PubMed  CAS  Google Scholar 

Yu M, Chen F, Wang H, Fu Q, Yan L, Chen Z, Li H, Jia M, Yang D, Hua X, et al. Endoplasmic reticulum stress mediates nickel chloride-induced epithelial-mesenchymal transition and migration of human lung cancer A549 cells through Smad2/3 and p38 MAPK activation. Ecotoxicol Environ Saf. 2023;249: 114398.

Article  PubMed  CAS  Google Scholar 

Koo JH, Lee HJ, Kim W, Kim SG. Endoplasmic reticulum stress in hepatic stellate cells promotes liver fibrosis via PERK-mediated degradation of HNRNPA1 and up-regulation of SMAD2. Gastroenterology. 2016;150(1):181-193.e188.

Article  PubMed  CAS  Google Scholar 

Yang Y, Liu Q, Li Z, Zhang R, Jia C, Yang Z, Zhao H, Ya S, Mao R, Ailijiang T, et al. GP73 promotes epithelial-mesenchymal transition and invasion partly by activating TGF-β1/Smad2 signaling in hepatocellular carcinoma. Carcinogenesis. 2018;39(7):900–10.

Article  PubMed  CAS  Google Scholar 

Yu S, Gao W, Zeng P, Chen C, Zhang Z, Liu Z, Liu J. Exploring the effect of Gupi Xiaoji prescription on hepatitis B virus-related liver cancer through network pharmacology and in vitro experiments. Biomed Pharmacother. 2021;139: 111612.

Article  PubMed  CAS  Google Scholar 

Neshat SY, Quiroz VM, Wang Y, Tamayo S, Doloff JC: Liver disease: induction, progression, immunological mechanisms, and therapeutic interventions. Int J Mol Sci 2021;22(13).

Li H, Yan L, Shi Y, Lv D, Shang J, Bai L, Tang H. Hepatitis B virus infection: overview. Adv Exp Med Biol. 2020;1179:1–16.

Article  PubMed  CAS  Google Scholar 

Iannacone M, Guidotti LG. Immunobiology and pathogenesis of hepatitis B virus infection. Nat Rev Immunol. 2022;22(1):19–32.

Article  PubMed  CAS  Google Scholar 

Li Y, He M, Wang Z, Duan Z, Guo Z, Wang Z, Gong R, Chu T, Cai J, Gao B. STING signaling activation inhibits HBV replication and attenuates the severity of liver injury and HBV-induced fibrosis. Cell Mol Immunol. 2022;19(1):92–107.

Article  PubMed  Google Scholar 

Xie H, Xie D, Zhang J, Jin W, Li Y, Yao J, Pan Z, Xie D. ROS/NF-κB signaling pathway-mediated transcriptional activation of TRIM37 promotes HBV-associated hepatic fibrosis. Mol Ther Nucleic Acids. 2020;22:114–23.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Xiang D, Zou J, Zhu X, Chen X, Luo J, Kong L, Zhang H. Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGF-β/Smad and YAP signaling. Phytomedicine. 2020;78: 153294.

Article  PubMed  CAS  Google Scholar 

Nakamura I, Asumda FZ, Moser CD, Kang YNN, Lai JP, Roberts LR: Sulfatase-2 regulates liver fibrosis through the TGF-β signaling pathway. Cancers (Basel) 2021;13(21).

Hossain MG, Ueda K. Regulation of hepatitis B virus replication by modulating endoplasmic reticulum stress (ER-stress). Int J Microbiol. 2024;2024:9117453.

Article  PubMed  PubMed Central  Google Scholar 

Li L, Guo ZY, Wang J, Fei PP, Ji YF, Xu CG. Tauroursodeoxycholic acid inhibits TGF-β1-induced renal fibrosis markers in cultured renal mesangial cells by regulating endoplasmic reticulum stress. Exp Ther Med. 2022;23(6):432.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shin JM, Kang JH, Park JH, Yang HW, Lee HM, Park IH: TGF-β1 activates nasal fibroblasts through the induction of endoplasmic reticulum stress. Biomol 2020;10(6).

Gatselis NK, Tornai T, Shums Z, Zachou K, Saitis A, Gabeta S, Albesa R, Norman GL, Papp M, Dalekos GN. Golgi protein-73: a biomarker for assessing cirrhosis and prognosis of liver disease patients. World J Gastroenterol. 2020;26(34):5130–45.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Liu Y, Zhang J, Zhai Z, Liu C, Yang S, Zhou Y, Zeng X, Liu J, Zhang X, Nie X, et al. Upregulated PrP(C) by HBx enhances NF-κB signal via liquid-liquid phase separation to advance liver cancer. NPJ Precis Oncol. 2024;8(1):211.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Zheng XS, Liu HJ, Zhang LL, Li H, Wang CJ, Xin YJ, Hao R. MiR-559 targets GP73 to suppress proliferation and invasion of hepatocellular carcinoma in vitro. Kaohsiung J Med Sci. 2020;36(10):793–8.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ye J, Gao X, Huang X, Huang S, Zeng D, Luo W, Zeng C, Lu C, Lu L, Huang H, et al. Integrating single-cell and spatial transcriptomics to uncover and elucidate GP73-mediated pro-angiogenic regulatory networks in hepatocellular carcinoma. Research (Wash D C). 2024;7:0387.

PubMed  CAS  Google Scholar 

Du H, Le G, Hou L, Mao X, Liu S, Huang K. Nontoxic concentration of ochratoxin A aggravates renal fibrosis induced by adriamycin/cyclosporine A nephropathy via TGF-β1/SMAD2/3. J Agric Food Chem. 2022;70(43):14005–14.

Article  PubMed  CAS  Google Scholar 

Sun Y, Liu B, Xie J, Jiang X, Xiao B, Hu X, Xiang J: Aspirin attenuates liver fibrosis by suppressing TGF-β1/Smad signaling. Mol Med Rep 2022;25(5).

Bao M, Feng Q, Zou L, Huang J, Zhu C, Xia W. Endoplasmic reticulum stress promotes endometrial fibrosis through the TGF-β/SMAD pathway. Reproduction. 2023;165(2):171–82.

Article  PubMed  CAS  Google Scholar 

Mu Z, Li B, Chen M, Liang C, Gu W, Su J: Endoplasmic reticulum stress induces renal fibrosis in high-fat diet mice via the TGF-β/SMAD pathway. Mol Med Rep 2024;30(6).

Fang J, Shu S, Dong H, Yue X, Piao J, Li S, Hong L, Cheng XW. Histone deacetylase 6 controls cardiac fibrosis and remodelling through the modulation of TGF-β1/Smad2/3 signalling in post-infarction mice. J Cell Mol Med. 2024;28(17): e70063.

Article  PubMed  PubMed Central  CAS 

Comments (0)

No login
gif