Downregulation of protein phosphatase 2A α in asthmatic airway smooth muscle

Am J Physiol Lung Cell Mol Physiol. 2024 Mar 26. doi: 10.1152/ajplung.00050.2024. Online ahead of print.ABSTRACTAirway smooth muscle cell (ASM) is renowned for its involvement in airway hyperresponsiveness through impaired ASM relaxation and bronchoconstriction in asthma which poses a significant challenge in the field. Recent studies have explored different targets in ASM to alleviate airway hyperresponsiveness, however, a sizeable portion of asthmatics still experience poor control. In our study, we explored protein phosphatase 2A (PP2A) in ASM as it has been reported to regulate cellular contractility by controlling intracellular calcium ([Ca2+]i), ion channels, and respective regulatory proteins. We obtained human ASM cells and lung tissues from healthy and asthmatic patients and evaluated PP2A expression using RNA Seq data, immunofluorescence, and immunoblotting. We further investigated the functional importance of PP2A by determining its role in bronchoconstriction using mouse bronchus and human ASM [Ca2+]i regulation. We found ubiquitous expression of PP2A isoforms in human ASM with PP2Aα being predominantly expressed. Interestingly, PP2Aα was significantly downregulated in asthmatic tissue and human ASM exposed to pro-inflammatory cytokines. Functionally, PP2Aα activation inhibited acetylcholine or methacholine induced bronchial contraction in mouse bronchus and further potentiated isoproterenol-induced bronchial relaxation. Mechanistically, PP2Aα activation inhib...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Source Type: research