2. Academic Validation
  3. Piezo1 promotes the progression of necrotizing enterocolitis by activating the Ca2(+)/CaMKII-dependent pathway

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

  • Commun Biol. 2025 Mar 12;8(1):417. doi: 10.1038/s42003-025-07821-6.
Zhenyu Li 1 2,  Qinlei Jiang 1 2,  Jiaqi Wei 1 2,  Dan Dang 1 2,  Zhaoli Meng 3,  Hui Wu 4 5
Affiliations

Affiliations

  • 1 Department of Neonatology, Children's Medical Center, The First Hospital of Jilin University, Changchun, Jilin, China.
  • 2 The Child Health Clinical Research Center of Jilin Province, Changchun, Jilin, China.
  • 3 Laboratory of Tumor Immunology, The First Hospital of Jilin University, Changchun, China.
  • 4 Department of Neonatology, Children's Medical Center, The First Hospital of Jilin University, Changchun, Jilin, China. wuhui@jlu.edu.cn.
  • 5 The Child Health Clinical Research Center of Jilin Province, Changchun, Jilin, China. wuhui@jlu.edu.cn.
PMID: 40074811 DOI: 10.1038/s42003-025-07821-6
Abstract

Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel necrosis of preterm infants with limited therapeutic approaches. Mounting evidence supports the role of Piezo1, namely, a widely distributed mechanosensor in intestinal epithelial cells (IECs), in intestinal inflammation but its underlying mechanism in the development of NEC remains unexplored. In this study, we demonstrated that Piezo1 expression was higher in preterm infants with lower gestational age. C57BL/6J mice wherein Piezo1 was deleted in IECs (villin-specific Piezo1 knockout mice; Piezo1flox/floxVillinCre+) and Piezo1flox/flox littermates were subjected to induce NEC, and Piezo1 knockout regulated the intestinal barrier function, restricted cytokines secretion, and diminished the inflammatory response in NEC mouse models. Piezo1 elevated cytosolic Ca2+ levels and activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) to promote the CaMKII/NF-κB interaction and NF-κB activation in vitro. Finally, the effects of a CaMKII inhibitor, KN93, were evaluated both in vitro and in vivo in NEC models, and the functions of Piezo1 in IECs were suppressed partially by KN93. In this study, we characterise the undefined role of Piezo1 in the development of NEC, which may partially be attributed to the differential role of calcium under pathophysiological conditions.

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