TY - JOUR
T1 - Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats
AU - Xia, Peng
AU - Deng, Qing
AU - Gao, Jin
AU - Yu, Xiaolan
AU - Zhang, Yang
AU - Li, Jingjing
AU - Guan, Wen
AU - Hu, Jianjun
AU - Tan, Quanhui
AU - Zhou, Liang
AU - Han, Wei
AU - Yuan, Yunsheng
AU - Yu, Yan
N1 - Funding Information:
This study was funded by a Science and Technology Program of Shanghai Grant , China ( 12431900600 ) and partly supported by the National Natural Science Foundation of China , China ( 81302825 to Y.Y.). All authors declare no conflicts of interest. All guidelines of the Animal Care and Use Committee of Shanghai Jiao Tong University , China for the care and use of animals were followed in this study. This article does not contain any experiments with human participants performed by any of the authors.
Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.
PY - 2016/5/15
Y1 - 2016/5/15
N2 - 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 0.5 mg/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.
AB - 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 0.5 mg/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.
KW - Anti-RAGE
KW - Bile duct ligation
KW - Hepatic stellate cell
KW - Liver fibrosis
KW - Liver injury
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U2 - 10.1016/j.ejphar.2016.03.017
DO - 10.1016/j.ejphar.2016.03.017
M3 - Article
C2 - 26970185
AN - SCOPUS:84961285389
SN - 0014-2999
VL - 779
SP - 102
EP - 110
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -