Extracellular stiffness and urinary bladder fibrosis
Fibrosis is a chronic inflammation process with excess extracellular matrix (ECM) deposition that cannot be reversed. Patients suffer from bladder dysfunction caused by bladder fibrosis. Moreover, the interactive mechanisms between ECM and bladder fibrosis are still obscure. Hence, we assessed the pivotal effect of Yes-associated protein (YAP) on the proliferation of bladder smooth muscle in fibrosis process. Sequencings and proteomics revealed that YAP bound to Smad3 and promoted the proliferation of hBdSMC via MAPK/ERK signalling pathway in stiff ECM. Moreover, CUT and TAG sequencing and dual-luciferase assays demonstrated that Smad3 inhibited the transcription of JUN. Collectively, YAP binding with Smad3 in the nucleus promoted the proliferation of bladder smooth muscle through the MAPK/ERK signalling pathway. The current study identified a novel mechanism of mechanical force induced bladder fibrosis that provided insights in YAP associated organ fibrosis.