Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts

Contraction of intestinal myofibroblasts (IMF) contributes to the development of strictures and fistulas seen in inflammatory bowel disease, but the mechanisms that regulate tension within these cells are poorly understood. In this study we investigated the role of nitric oxide (NO) signaling in C-t...

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Main Authors: Yishi Chen, Taned Chitapanarux, Jianfeng Wu, Russell K. Soon, Andrew C. Melton, Hal F. Yee
Format: Journal
Published: 2018
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84878145650&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/47871
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-478712018-04-25T08:45:02Z Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts Yishi Chen Taned Chitapanarux Jianfeng Wu Russell K. Soon Andrew C. Melton Hal F. Yee Contraction of intestinal myofibroblasts (IMF) contributes to the development of strictures and fistulas seen in inflammatory bowel disease, but the mechanisms that regulate tension within these cells are poorly understood. In this study we investigated the role of nitric oxide (NO) signaling in C-type natriuretic peptide (CNP)-induced relaxation of IMF. We found that treatment with ODQ, a soluble guanylyl cyclase (sGC) inhibitor, or NG-nitro-L-arginine (L-NNA) or NG-monomethyl-L-arginine (L-NMMA), inhibitors of NO production, all impaired the relaxation of human and mouse IMF in response to CNP. ODQ, L-NNA, and L-NMMA also prevented CNP-induced elevations in cGMP concentrations, and L-NNA or L-NMMA blocked CNP-induced decreases in myosin light phosphorylation. IMF isolated from transgenic mice deficient in inducible nitric oxide synthase (iNOS) had reduced relaxation responses to CNP compared with IMF from control mice and were insensitive to the effects of ODQ, L-NNA, and L-NMMA on CNP treatment. Together these data indicate that stimulation of sGC though NO produced by iNOS activation is required for maximal CNP-induced relaxation in IMF. © 2013 the American Physiological Society. 2018-04-25T08:45:02Z 2018-04-25T08:45:02Z 2013-06-07 Journal 15221547 01931857 2-s2.0-84878145650 10.1152/ajpgi.00214.2012 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84878145650&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/47871
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description Contraction of intestinal myofibroblasts (IMF) contributes to the development of strictures and fistulas seen in inflammatory bowel disease, but the mechanisms that regulate tension within these cells are poorly understood. In this study we investigated the role of nitric oxide (NO) signaling in C-type natriuretic peptide (CNP)-induced relaxation of IMF. We found that treatment with ODQ, a soluble guanylyl cyclase (sGC) inhibitor, or NG-nitro-L-arginine (L-NNA) or NG-monomethyl-L-arginine (L-NMMA), inhibitors of NO production, all impaired the relaxation of human and mouse IMF in response to CNP. ODQ, L-NNA, and L-NMMA also prevented CNP-induced elevations in cGMP concentrations, and L-NNA or L-NMMA blocked CNP-induced decreases in myosin light phosphorylation. IMF isolated from transgenic mice deficient in inducible nitric oxide synthase (iNOS) had reduced relaxation responses to CNP compared with IMF from control mice and were insensitive to the effects of ODQ, L-NNA, and L-NMMA on CNP treatment. Together these data indicate that stimulation of sGC though NO produced by iNOS activation is required for maximal CNP-induced relaxation in IMF. © 2013 the American Physiological Society.
format Journal
author Yishi Chen
Taned Chitapanarux
Jianfeng Wu
Russell K. Soon
Andrew C. Melton
Hal F. Yee
spellingShingle Yishi Chen
Taned Chitapanarux
Jianfeng Wu
Russell K. Soon
Andrew C. Melton
Hal F. Yee
Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts
author_facet Yishi Chen
Taned Chitapanarux
Jianfeng Wu
Russell K. Soon
Andrew C. Melton
Hal F. Yee
author_sort Yishi Chen
title Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts
title_short Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts
title_full Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts
title_fullStr Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts
title_full_unstemmed Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts
title_sort inducible nos mediates cnp-induced relaxation of intestinal myofibroblasts
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84878145650&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/47871
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