The Role of KCNMB1 and BK Channels in Myofibroblast Differentiation and Pulmonary Fibrosis.

The Role of KCNMB1 and BK Channels in Myofibroblast Differentiation and Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2019 Sep 05;: Authors: Scruggs AM, Grabauskas G, Huang SK Abstract The differentiation of fibroblasts to myofibroblasts is critical to the development of fibrotic disorders, including idiopathic pulmonary fibrosis (IPF). Previously, we demonstrated that fibroblasts from patients with IPF exhibit changes in DNA methylation across the genome that contribute to a pro-fibrotic phenotype. One of the top differentially methylated genes identified in our previous study was KCNMB1, which codes for the beta subunit of the large conductance potassium channel (BK, MaxiK, KCa1.1). Here, we examine how the expression of KCNMB1 differs in IPF fibroblasts compared to normal cells, and how BK channels affect myofibroblast differentiation. Fibroblasts from patients with IPF exhibited increased expression of KCNMB1, which corresponds to increased DNA methylation within the gene body. Patch clamp experiments demonstrated that IPF fibroblasts exhibit increased BK channel activity. Knock down of KCNMB1 attenuated the ability of fibroblasts to contract collagen gels, and this was associated with a loss of α-smooth muscle actin (SMA) expression. Pharmacologic activation of BK channels stimulated α-SMA expression, whereas BK channel inhibitors blocked the upregulation of α-SMA. The ability of BK channels to enhance α-SMA expression was ...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research