University of Leicester
The K+ channel KCa3.1 as a novel target for idiopathic pulmonary fibrosis..pdf (2.67 MB)

The K[superscript: +] channel K[subscript: Ca]3.1 as a novel target for idiopathic pulmonary fibrosis.

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posted on 2015-07-20, 09:34 authored by Katy Morgan Roach, Stephen Mark Duffy, W. Coward, C. Feghali-Bostwick, H. Wulff, Peter Bradding
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.



PLoS One, 2013, 8 (12), e85244

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/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation


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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