Our results showed that ECM stiffness could promote excessive secretion of ECM by MCs through the Piezo1-p38MAPK-YAP signaling pathway, in addition, the Piezo1-p38MAPK-YAP signaling pathway have been verified play a role in the animal model of renal fibrosis induced by UUO and targeting mechanosensitive Piezo1 attenuates the progression of renal fibrosis. The gene discussed is PIEZO1; the disease is renal fibrosis.