Calcium/P53/Ninjurin 1 Signaling Mediates Plasma Membrane Rupture of Acinar Cells in Severe Acute Pancreatitis.

ABSTRACT: Ninjurin 1 (NINJ1) is a double-transmembrane cell-surface protein that might mediate plasma membrane rupture (PMR) and the diffusion of inflammatory factors. PMR is a characteristic of acinar cell injury in severe acute pancreatitis (SAP). However, the involvement of NINJ1 in mediating the PMR of acinar cells in SAP is currently unclear. Our study has shown that NINJ1 is expressed in acinar cells, and the expression is significantly upregulated in sodium-taurocholate-induced SAP. The knockout of NINJ1 delays PMR in acinar cells and alleviates SAP. Moreover, we observed that NINJ1 expression is mediated by Ca²⁺ concentration in acinar cells. Importantly, we found that Ca²⁺ overload drives mitochondrial stress to upregulate the P53/NINJ1 pathway, inducing PMR in acinar

SUBMITTER: Lee C 

PROVIDER: S-EPMC10380776 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature