PMID- 25088816 OWN - NLM STAT- MEDLINE DCOM- 20150605 LR - 20220408 IS - 1872-7484 (Electronic) IS - 1566-0702 (Linking) VI - 185 DP - 2014 Oct TI - Does hepatic vagus nerve modulate the progression of biliary fibrosis in rats? PG - 67-75 LID - S1566-0702(14)00099-X [pii] LID - 10.1016/j.autneu.2014.07.005 [doi] AB - Recent studies have shown that vagus nerve activation inhibits cytokine production in a variety of non-neural cells though activation of alpha7 nicotinic acetylcholine receptor (alpha7nAChR). 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. alpha7nAChR expression was assessed using RT-PCR as well as immunostaining. RT-PCR analysis of the liver showed that alpha7nAChR mRNA is expressed in rat liver. Immunostaining study demonstrated that hepatic alpha7nAChR is mainly expressed in the hepatocytes of cirrhotic liver with minimum alpha7nAChR 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 alpha7nAChR 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. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Hajiasgharzadeh, Khalil AU - Hajiasgharzadeh K AD - Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. FAU - Tavangar, Seyed Mohammad AU - Tavangar SM AD - Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Javan, Mohammad AU - Javan M AD - Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. FAU - Dehpour, Ahmad R AU - Dehpour AR AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. FAU - Mani, Ali R AU - Mani AR AD - Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: mani@modares.ac.ir. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140717 PL - Netherlands TA - Auton Neurosci JT - Autonomic neuroscience : basic & clinical JID - 100909359 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Nicotinic Antagonists) RN - 0 (RNA, Messenger) RN - 0 (TIMP1 protein, rat) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 0 (alpha7 Nicotinic Acetylcholine Receptor) RN - 21019-30-7 (methyllycaconitine) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - X8YN71D5WC (Aconitine) SB - IM MH - Aconitine/analogs & derivatives/pharmacology MH - Animals MH - Aspartate Aminotransferases/blood MH - Chemokine CCL2/metabolism MH - Disease Models, Animal MH - Disease Progression MH - Epithelium/drug effects/pathology/physiopathology MH - Hepatocytes/drug effects/metabolism/pathology MH - Liver/drug effects/pathology/physiopathology MH - Liver Cirrhosis, Biliary/drug therapy/pathology/*physiopathology/surgery MH - Male MH - Myofibroblasts/drug effects/pathology/physiology MH - Nicotinic Antagonists/pharmacology MH - RNA, Messenger/metabolism MH - Rats, Sprague-Dawley MH - Tissue Inhibitor of Metalloproteinase-1/metabolism MH - Vagotomy MH - Vagus Nerve/drug effects/pathology/*physiopathology MH - alpha7 Nicotinic Acetylcholine Receptor/antagonists & inhibitors/*metabolism OTO - NOTNLM OT - Cirrhosis OT - Fibrosis OT - Inflammation OT - Vagus nerve OT - alpha7 nicotinic acetylcholine receptor EDAT- 2014/08/05 06:00 MHDA- 2015/06/06 06:00 CRDT- 2014/08/05 06:00 PHST- 2014/04/16 00:00 [received] PHST- 2014/06/23 00:00 [revised] PHST- 2014/07/12 00:00 [accepted] PHST- 2014/08/05 06:00 [entrez] PHST- 2014/08/05 06:00 [pubmed] PHST- 2015/06/06 06:00 [medline] AID - S1566-0702(14)00099-X [pii] AID - 10.1016/j.autneu.2014.07.005 [doi] PST - ppublish SO - Auton Neurosci. 2014 Oct;185:67-75. doi: 10.1016/j.autneu.2014.07.005. Epub 2014 Jul 17.