Proprotein convertase inhibition promotes ciliated cell differentiation - a potential mechanism for the inhibition of Notch1 signalling by decanoyl-RVKR-chloromethylketone.

ABSTRACT: Chronic repetitive rounds of injury and repair in the airway lead to airway remodelling, including ciliated cell loss and mucous cell hyperplasia. Airway remodelling is mediated by many growth and differentiation factors including Notch1, which are proteolytically processed by proprotein convertases (PCs). The present study evaluated a novel approach for controlling basal cell-type determination based on the inhibition of PCs. It was found that decanoyl-RVKR-chloromethylketone (CMK), a PC inhibitor, promotes ciliated cell differentiation and has no effect on the ciliary beat frequency in air-liquid interface (ALI) cultures of human nasal epithelial cells (HNECs). Comparative microarray analysis revealed that CMK considerably increases ciliogenesis-related gene expression. Use of cell-perme

SUBMITTER: Lee SN 

PROVIDER: S-EPMC6214225 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature