Discoidin domain receptor 1 contributes to the survival of lung fibroblast in idiopathic pulmonary fibrosis

The American Journal of Pathology
Wataru MatsuyamaKimiyoshi Arimura

Abstract

Idiopathic pulmonary fibrosis (IPF), characterized by fibroblast proliferation and accumulation of extracellular matrix, including collagen, is a chronic progressive disorder that results in lung remodeling and fibrosis. However, the cellular mechanisms that may make fibroblasts resistant to apoptosis have not been completely elucidated. Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase whose ligand is collagen, is expressed in vivo and contributes in vitro to leukocyte differentiation and nuclear factor (NF)-kappaB activation, which may play an important role in fibroblast survival. In this study, we examined in vivo and in vitro DDR1 expression and its role in cell survival using fibroblasts obtained from IPF and non-IPF patients. Immunohistochemically, fibroblasts present in fibroblastic foci expressed endogenous DDR1. The DDR1 expression level was significantly higher in fibroblasts from IPF patients, and the predominant isoform was DDR1b. In IPF patients, DDR1 activation in fibroblasts inhibited Fas ligand-induced apoptosis and resulted in NF-kappaB nuclear translocation. Suppression of DDR1 expression in fibroblasts by siRNA abolished these effects, and an NF-kappaB inhibitor abrogated the anti-apoptotic effe...Continue Reading

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Citations

Dec 30, 2006·Seminars in Respiratory and Critical Care Medicine·Jeffrey C Horowitz, Victor J Thannickal
Dec 22, 2007·American Journal of Respiratory and Critical Care Medicine·Andrés F MuroEric S White
Dec 23, 2008·American Journal of Respiratory Cell and Molecular Biology·Adrian G Rosas-TaracoMercedes González-Juarrero
Oct 30, 2007·The Journal of Clinical Investigation·William J BurlinghamDavid S Wilkes
Feb 4, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Daniela De StefanoRosa Carnuccio
Mar 15, 2013·Expert Opinion on Investigational Drugs·Sushmita ChakrabortyAbhijit Ray
Nov 15, 2008·Journal of Molecular Biology·Cosmin MihaiGunjan Agarwal
Oct 9, 2007·Archivos de bronconeumología·María Molina-MolinaAntoni Xaubet
Apr 18, 2007·Clinical and Experimental Immunology·T TairaK Arimura
Feb 6, 2007·Journal of Molecular Biology·Gunjan AgarwalDaniel F Iscru
Sep 28, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sara Melboucy-BelkhirLaurent Plantier
Jul 11, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Junjie GaoCanghui Guo

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