title: Does hepatic vagus nerve modulate the progression of biliary fibrosis in rats?
abstract: Recent studies have shown that vagus nerve activation inhibits cytokine production in a variety of non-neural cells though activation of α7 nicotinic acetylcholine receptor (α7nAChR). Since chronic inflammation plays a pivotal role in liver fibrosis, this study was designed to investigate the role of hepatic vagus nerve in the progression of hepatic fibrosis in rats. Cirrhosis was induced by chronic ligation of the bile duct. Hepatic hydroxyproline level, portal pressure, serum transaminase level, hepatic TIMP-1 (tissue inhibitor of metalloproteinase-1) and MCP-1 (monocyte chemoattractant peptide-1) expression were measured in order to assess the progression of liver cirrhosis. α7nAChR expression was assessed using RT-PCR as well as immunostaining. RT-PCR analysis of the liver showed that α7nAChR mRNA is expressed in rat liver. Immunostaining study demonstrated that hepatic α7nAChR is mainly expressed in the hepatocytes of cirrhotic liver with minimum α7nAChR expression in biliary epithelium or myofibroblasts. Bile duct ligation was associated with portal hypertension, increased hepatic hydroxyproline level as well as TIMP-1 and MCP-1 expression in the liver. However neither selective hepatic vagotomy nor methyllycaconitine (an α7nAChR antagonist) could significantly affect development of portal hypertension or hepatic fibrosis in rats. Selective hepatic vagotomy could only attenuate serum aspartate aminotransferase level in bile duct ligated rats but did not have a significant effect on hepatic inflammation as assessed by MCP-1 mRNA expression. Our study provides evidence against a crucial role for the hepatic vagus nerve as an intrinsic protective mechanism in modulation of hepatic fibrosis in a rat model of biliary cirrhosis.
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Hajiasgharzadeh
authors.affiliation: Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Tavangar
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: mani@modares.ac.ir.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Mani
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D008297:Male; D058628:Myofibroblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018733:Nicotinic Antagonists; D012333:RNA, Messenger; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D001219:Aspartate Aminotransferases; D000157:Aconitine
keywords: Cirrhosis; Fibrosis; Inflammation; Vagus nerve; α7 nicotinic acetylcholine receptor