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Title: The K[superscript: +] channel K[subscript: Ca]3.1 as a novel target for idiopathic pulmonary fibrosis.
Authors: Roach, Katy Morgan
Duffy, Stephen Mark
Coward, W.
Feghali-Bostwick, C.
Wulff, H.
Bradding, Peter
First Published: 31-Dec-2013
Publisher: Public Library of Science
Citation: PLoS One, 2013, 8 (12), e85244
Abstract: BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a common, progressive and invariably lethal interstitial lung disease with no effective therapy. We hypothesised that K[subscript: Ca]3.1 K[superscript: +] channel-dependent cell processes contribute to IPF pathophysiology. METHODS: K[subscript: Ca]3.1 expression in primary human lung myofibroblasts was examined using RT-PCR, western blot, immunofluorescence and patch-clamp electrophysiology. The role of K[subscript: Ca]3.1 channels in myofibroblast proliferation, wound healing, collagen secretion and contraction was examined using two specific and distinct K[subscript: Ca]3.1 blockers (TRAM-34 and ICA-17043 [Senicapoc]). RESULTS: Both healthy non fibrotic control and IPF-derived human lung myofibroblasts expressed K[subscript: Ca]3.1 channel mRNA and protein. K[subscript: Ca]3.1 ion currents were elicited more frequently and were larger in IPF-derived myofibroblasts compared to controls. K[subscript: Ca]3.1 currents were increased in myofibroblasts by TGFβ1 and basic FGF. K[subscript: Ca]3.1 was expressed strongly in IPF tissue. K[subscript: Ca]3.1 pharmacological blockade attenuated human myofibroblast proliferation, wound healing, collagen secretion and contractility in vitro, and this was associated with inhibition of TGFβ1-dependent increases in intracellular free Ca[superscript: 2+]. CONCLUSIONS: K[subscript: Ca]3.1 activity promotes pro-fibrotic human lung myofibroblast function. Blocking K[subscript: Ca]3.1 may offer a novel approach to treating IPF with the potential for rapid translation to the clinic.
DOI Link: 10.1371/journal.pone.0085244
eISSN: 1932-6203
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2013 Roach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: Correction: 16 Jan 2014: Roach KM, Duffy SM, Coward W, Feghali-Bostwick C, Wulff H, et al. (2014) Correction: The K+ Channel KCa3.1 as a Novel Target for Idiopathic Pulmonary Fibrosis. PLoS ONE 9(1): 10.1371/annotation/790e86f8-3506-49d6-b7d0-7dbbc580d808. doi: 10.1371/annotation/790e86f8-3506-49d6-b7d0-7dbbc580d808
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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