Piezo1 promotes the progression of necrotizing enterocolitis via activating Ca2(+)/CaMKII-dependent pathway

Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel necrosis of very preterm infants with limited therapeutic approaches. Mounting evidence supports the role of Piezo1, a widely distributed mechanosensor on intestinal epithelial cells (IECs), in intestinal inflammation, but its underlying mechanism in the development of NEC has not been explored. Here we demonstrated that Piezo1 protein expression was higher in very preterm infants compared to full-term infants, and positively associated with serum inflammation levels in NEC patients. C57BL/6J mice in which Piezo1 was selectively deleted IECs (villin specific knockout; CKO) and floxed control mice were subjected to induce NEC, and Piezo1 regulated intestinal barrier function, restricted cytokines secretion, and diminished the inflammatory response in NEC mouse models. RNA-seq profiling of small intestine fromC57BL/6J mice with IEC-specific Piezo1 knockout (CKO) and their floxed control mice, including NEC-induced and control groups.