Mitochondrial DNA Leakage Promotes Persistent Pancreatic Acinar Cell Injury in Acute Pancreatitis via the cGAS-STING-NF-κB Pathway.

IF 4.5 2区 医学 Q2 CELL BIOLOGY
Deyu Zhang, Jiayu Li, Linlin Zhao, Zhenghui Yang, Chang Wu, Yue Liu, Wanshun Li, Zhendong Jin, Jiayi Ma
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Abstract

Previous research has shown that the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in macrophages can promote severe acute pancreatitis through the release of inflammatory factors. The role of this pathway in pancreatic acinar cells, however, has not been studied, and understanding its mechanism could be crucial. We analysed plasma from 50 acute pancreatitis (AP) patients and 10 healthy donors using digital PCR, which links mitochondrial DNA (mtDNA) levels to the severity of AP. Single-cell sequencing of the pancreas during AP revealed differentially expressed genes and pathways in acinar cells. Experimental studies using mouse and cell models, which included mtDNA staining and quantitative PCR, revealed mtDNA leakage and the activation of STING-related pathways, indicating potential inflammatory mechanisms in AP. In conclusion, our study revealed that the mtDNA-STING-nuclear factor κB(NF-κB) pathway in pancreatic acinar cells could be a novel pathogenic factor in AP.

Abstract Image

线粒体 DNA 泄漏通过 cGAS-STING-NF-κB 通路促进急性胰腺炎中胰腺针叶细胞的持续损伤
以往的研究表明,巨噬细胞中环GMP-AMP合成酶(cGAS)-干扰素基因刺激器(STING)通路的激活可通过释放炎症因子促进重症急性胰腺炎的发生。然而,该通路在胰腺尖锐细胞中的作用尚未得到研究,因此了解其机制至关重要。我们使用数字 PCR 分析了 50 名急性胰腺炎(AP)患者和 10 名健康捐献者的血浆,该方法将线粒体 DNA(mtDNA)水平与急性胰腺炎的严重程度联系起来。对急性胰腺炎期间的胰腺进行单细胞测序,发现了尖腺细胞中表达不同的基因和通路。使用小鼠和细胞模型(包括 mtDNA 染色和定量 PCR)进行的实验研究显示,mtDNA 泄漏和 STING 相关通路的激活表明 AP 存在潜在的炎症机制。总之,我们的研究揭示了胰腺尖腺细胞中的mtDNA-STING-核因子κB(NF-κB)通路可能是AP的一个新的致病因素。
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来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
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