title: Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats.
abstract: Cholestasis leads to acute hepatic injury, fibrosis/cirrhosis, inflammation, and duct proliferation. We investigated whether blocking receptor of advanced glycation end-products (RAGE) with polyclonal anti-RAGE antibodies (anti-RAGE) could regulate acute liver injury and fibrosis in a rat bile duct ligation (BDL) model. Male Wister rats received 0.5mg/kg rabbit anti-RAGE or an equal amount of rabbit IgG by subcutaneous injection twice a week after BDL. Samples of liver tissue and peripheral blood were collected at 14 days after BDL. Serum biochemistry and histology were used to analyze the degree of liver injury. Quantitative real-time PCR (qPCR) and immunohistochemical staining were used to further analyze liver injury. Anti-RAGE improved the gross appearance of the liver and the rat survival rate. Liver tissue histology and relevant serum biochemistry indicated that anti-RAGE attenuated liver necrosis, inflammation, liver fibrosis, and duct proliferation in the BDL model. qPCR and western blotting showed significant reductions in interleukin-1β expression levels in the liver by treatment with anti-RAGE. Anti-RAGE also significantly reduced the mRNA levels of α1(1) collagen (Col1α1) and cholesterol 7α-hydroxylase, and the ratio of tissue inhibitor of matrix metalloproteinase-1 to matrix metalloproteinases (MMPs) in the liver. In addition, anti-RAGE regulated the transcriptional level of Col1α1 and MMP-9 in transforming growth factor-β-induced activated LX-2 cells in vitro. Anti-RAGE was found to inhibit hepatic stellate cell proliferation in vivo and in vitro. Therefore, anti-RAGE can protect the liver from injury induced by BDL in rats.
authors.affiliation: Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.affiliation: Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Laboratory of Regenerative Medicine, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Laboratory of Regenerative Medicine, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Regenerative Medicine, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Guan
authors.affiliation: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd., Xuhui, Shanghai 200233, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd., Xuhui, Shanghai 200233, China.
authors.forename: Quanhui
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Laboratory of Regenerative Medicine, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Laboratory of Regenerative Medicine, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China; Engineering Research Center of Cell and Therapeutic Antibody, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China. Electronic address: yunsheng@sjtu.edu.cn.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Rd., Minhang, Shanghai 200240, China. Electronic address: yanyu@sjtu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D000941:Antigens / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002779:Cholestasis / Q000150:complications*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics; D008099:Liver / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000276:immunology*; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D000906:Antibodies; D000941:Antigens; D053583:Interleukin-1beta; D000067759:Receptor for Advanced Glycation End Products; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases
keywords: Anti-RAGE; Bile duct ligation; Hepatic stellate cell; Liver fibrosis; Liver injury; Vitamin K1 (PubChem CID: 5284607)