Inhibition of the KCa3.1 channel alleviates established pulmonary fibrosis in a large animal model

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease of increasing prevalence marked by poor prognosis and limited treatment options. Ca21-activated KCa3.1 potassium channels have been shown to play a key role in the aberrant activation and responses to injury in both epithelial cells and fibroblasts, both considered key drivers in the fibrotic process of IPF. Pharmacological inhibition of IPF-derived fibroblasts is able to somewhat prevent TGF-b- and basic fibroblast growth factor-dependent profibrotic responses. In the current study, we investigated whether blockade of theKCa3.1 ion channel in vivo with a selective inhibitor, Senicapoc, was able to attenuate both histologi..