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. Overall design: 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.

坏死性小肠结肠炎（Necrotizing enterocolitis, NEC）是一类发生于极早早产儿的致死性炎症性肠坏死疾病，目前临床治疗手段极为有限。越来越多的研究证据表明，广泛分布于肠上皮细胞（intestinal epithelial cells, IECs）的机械感受器Piezo1在肠道炎症进程中发挥关键作用，但其在NEC发生发展中的具体调控机制尚未被阐明。本研究证实，极早早产儿体内的Piezo1蛋白表达水平显著高于足月婴儿，且与NEC患者的血清炎症指标水平呈正相关。我们构建了肠上皮细胞特异性Piezo1敲除（绒毛蛋白特异性敲除，CKO）的C57BL/6J小鼠及对应的floxed对照小鼠，并对其诱导NEC模型，结果显示Piezo1可调节NEC小鼠模型的肠屏障功能、抑制细胞因子分泌并减轻肠道炎症反应。实验设计：对肠上皮细胞特异性Piezo1敲除（CKO）的C57BL/6J小鼠及其floxed对照小鼠的小肠组织开展RNA测序（RNA-seq）转录组分析，样本涵盖NEC诱导组与空白对照组。