Nuclear Factor-κB Increases Intracellular Calcium by Upregulation of Na+-Ca2+ Exchanger 1 in Cerulein-Induced Acute Pancreatitis

在 Cerulein 诱发的急性胰腺炎中,核因子 κB 通过上调 Na+-Ca2+ 交换器 1 增加细胞内钙

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作者:Yuyang Chen, Wanling Li, Rui Xie, Bo Tang, YuFeng Xiao, Feng Yang, Siyuan Chen, Senyuan Yu, Shiming Yang, Hui Dong, Hong Guo, Jing-Jing Liu

Conclusions

Our findings reveal a regulatory pathway through NF-κB/NCX1 governing Ca overload in AP development, thus providing potential targets for AP treatment.

Methods

To establish a rat model of AP induction, cerulein or L-arginine were intraperitoneally injected and tissue was histologically analyzed by hematoxylin and eosin staining. A cell culture-based model for AP induction was similarly created through cerulein treatment of AR42J cells. Induction of AP was also examined following exposure to the NXC1-targeted inhibitor KB-R7943. The expression of each gene was detected by Western blotting, immunofluorescence, immunohistochemistry, or quantitative reverse transcription polymerase chain reaction. Transcriptional regulation by nuclear factor (NF)-κB was detected using an NCX1 promoter-fusion dual luciferase reporter system. Cytosolic Ca was measured using a fluorescent calcium indicator.

Results

We found that cerulein induced NCX1 expression via activation of nuclear factor NF-κB, which potentially binds to the NCX1 promoter to induce its transcription. Conclusions: Our findings reveal a regulatory pathway through NF-κB/NCX1 governing Ca overload in AP development, thus providing potential targets for AP treatment.

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