Role of ZIP kinase in development of myofibroblast differentiation from HPMCs

Am J Physiol Lung Cell Mol Physiol. 2024 Jan 22. doi: 10.1152/ajplung.00251.2023. Online ahead of print.ABSTRACTDuring the development of pleural fibrosis, pleural mesothelial cells (PMCs) undergo phenotypic switching from differentiated mesothelial cells to mesenchymal cells (MesoMT). Here, we investigated how external stimuli such as TGF-β induce HPMC-derived myofibroblast differentiation to facilitate the development of pleural fibrosis. TGF- significantly increased di-phosphorylation but not mono-phosphorylation of myosin II regulatory light chain (RLC) in HPMCs. An increase in RLC di-phosphorylation was also found at the pleural layer of our carbon black bleomycin (CBB) pleural fibrosis mouse model, where it showed filamentous localization that coincided with αSMA in the cells in the pleura. Among the protein kinases that can phosphorylate myosin II RLC, ZIPK (zipper-interacting kinase) protein expression was significantly augmented after TGF-β stimulation. Further, ZIPK gene silencing attenuated RLC di-phosphorylation, suggesting that ZIPK is responsible for di-phosphorylation of myosin II in HPMCs. While TGF-β significantly increased expression of ZIP kinase protein, change in ZIP kinase mRNA was marginal, suggesting a post transcriptional mechanism for the regulation of post-transcriptional regulation of ZIP kinase expression by TGF-β. ZIPK gene knock-down (KD) also significantly reduced TGF-β induced up-regulation of αSMA expression. This finding suggests t...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Source Type: research