Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by Ca 2+ -dependent calpain/HIF-1α/Notch signaling

-dependent calpain signaling, which critically upregulates HIF-1α signaling. This key pathway subsequently influences the Notch and CCL2/CCR2 pathways, driving the polarization of M1 macrophages. In conclusion, our findings elucidate the biological functions of Piezo1 in renal macrophages, underscoring its role as a crucial mediator of acute kidney injury. Consequently, the genetic or pharmacological inhibition of Piezo1 presents a promising strategy for treating IR-AKI.