P30 PIEZO1 – a role in cardiac fibroblast differentiation?

Background Cardiac fibroblasts (CF) are responsible for extracellular matrix turnover, which is crucial in preserving the structural integrity of the myocardium. Mechanical signals initiate a phenotypic change in fibroblasts, triggering their differentiation into myofibroblasts. Piezo1, a recently discovered mechanically-activated non-selective cation channel, is important in converting mechanical signals into changes in cell function, such as migration and alignment. The Piezo1 protein and its role in the heart has yet to be investigated. We are investigating whether Piezo1 has a role in sensing mechanical stress in CF. Methods and Results Using RT-PCR, it was confirmed that both cultured and freshly isolated murine CF and cultured human CF express Piezo1. Furthermore, Piezo1 gene expression was modulated by cytokines which influence the fibroblast-to-myofibroblast differentiation pathway. Piezo1 was shown to be functional in cultured murine CF. Using an intracellular calcium measurement assay, it was demonstrated that these cells can be activated by a novel Piezo1 agonist. Furthermore, knockdown of Piezo1 by targeted siRNA decreased Piezo1 mRNA in cultured CF and reduced the effects of the Piezo1 agonist. Conclusion These data show that functional Piezo1 is expressed by CF and its expression can be affected by external stimuli, suggesting a correlation between Piezo1 expression and myofibroblast differentiation. Exploring this further will provide more understanding of this ion channel in CF function. Supported by The British Heart Foundation.