AIM: To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis. METHODS: In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells (HSC) were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin (AGE-BSA) and N(epsilon)-(carboxymethyl) lysine (CML)-BSA, or with tumor necrosis factor-alpha (TNF-alpha). In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS: In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-alpha. RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen alpha1(I) mRNA by AGE-BSA. CONCLUSION: Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.
AIM: To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis. METHODS: In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells (HSC) were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin (AGE-BSA) and N(epsilon)-(carboxymethyl) lysine (CML)-BSA, or with tumor necrosis factor-alpha (TNF-alpha). In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS: In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-alpha. RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen alpha1(I) mRNA by AGE-BSA. CONCLUSION: Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.
Authors: Francesco Cipollone; Annalisa Iezzi; Maria Fazia; Mirco Zucchelli; Barbara Pini; Chiara Cuccurullo; Domenico De Cesare; Giovanni De Blasis; Raffaella Muraro; Roberto Bei; Francesco Chiarelli; Ann Marie Schmidt; Franco Cuccurullo; Andrea Mezzetti Journal: Circulation Date: 2003-08-11 Impact factor: 29.690
Authors: Shan Zeng; Nikki Feirt; Michael Goldstein; James Guarrera; Nikalesh Ippagunta; Udeme Ekong; Hao Dun; Yan Lu; Wu Qu; Ann Marie Schmidt; Jean C Emond Journal: Hepatology Date: 2004-02 Impact factor: 17.425
Authors: A Casini; M Pinzani; S Milani; C Grappone; G Galli; A M Jezequel; D Schuppan; C M Rotella; C Surrenti Journal: Gastroenterology Date: 1993-07 Impact factor: 22.682
Authors: Guellue Cataldegirmen; Shan Zeng; Nikki Feirt; Nikalesh Ippagunta; Hao Dun; Wu Qu; Yan Lu; Ling Ling Rong; Marion A Hofmann; Thomas Kislinger; Sophia I Pachydaki; Daniel G Jenkins; Alan Weinberg; Jay Lefkowitch; Xavier Rogiers; Shi Fang Yan; Ann Marie Schmidt; Jean C Emond Journal: J Exp Med Date: 2005-02-07 Impact factor: 14.307
Authors: Ali Dehnad; Weiguo Fan; Joy X Jiang; Sarah R Fish; Yuan Li; Suvarthi Das; Gergely Mozes; Kimberly A Wong; Kristin A Olson; Gregory W Charville; Mohammed Ali; Natalie J Török Journal: J Clin Invest Date: 2020-08-03 Impact factor: 14.808
Authors: Christopher Leung; Chandana B Herath; Zhiyuan Jia; Sof Andrikopoulos; Bronwyn E Brown; Michael J Davies; Leni R Rivera; John B Furness; Josephine M Forbes; Peter W Angus Journal: World J Gastroenterol Date: 2016-09-21 Impact factor: 5.742