TAGLN2通过Kupffer细胞介导的炎症反应增加肝细胞焦亡,从而加重急性胰腺炎诱导的肝损伤。

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2025-06-05 eCollection Date: 2025-01-01 DOI:10.2478/aite-2025-0014
Huigeng Zhao, Yalan Luo, Xi Chen, Ju Wu, Zizhao Zhu, Hailong Chen
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引用次数: 0

摘要

焦亡是炎症细胞死亡的一种程序化形式,已被证明参与急性胰腺炎(AP)及其并发症肝损伤。Transgelin-2 (TAGLN2)是一种参与炎症反应的肌动蛋白结合蛋白,据报道在AP中高表达。然而,TAGLN2在AP诱导的肝损伤中的作用尚不清楚。在体内用蓝蛋白处理小鼠建立AP模型,用脂多糖(LPS)刺激Kupffer细胞模拟体外模型。通过一系列体外和体内实验,探讨TAGLN2在ap诱导的肝损伤中的作用和机制。给药后引起胰腺和肝脏组织病理损伤,淀粉酶、脂肪酶、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平升高。在AP小鼠肝细胞和库普弗细胞中,TAGLN2的转录和翻译水平均显著升高。敲除TAGLN2通过降低炎症细胞因子水平、焦热相关蛋白表达和肝功能障碍标志物来减轻肝损伤。在体外模型中,lps诱导的Kupffer细胞中炎症因子的相对水平、焦亡相关蛋白的表达和焦亡率升高,而TAGLN2敲除逆转了这些变化。在机制上,TAGLN2促进Kupffer细胞中ANXA2/NF-κB轴的激活,促进炎症反应。TAGLN2通过Kupffer细胞介导的ANXA2/NF-κB轴的炎症激活,增强肝细胞焦亡,从而加重ap诱导的肝损伤。靶向TAGLN2可能为减轻AP肝损伤提供潜在的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
TAGLN2 Exacerbates Acute Pancreatitis-Induced Liver Injury by Increasing Hepatocyte Pyroptosis via Kupffer Cells-Mediated Inflammatory Response.

Pyroptosis, a programmed form of inflammatory cell death, has been demonstrated to participate in both Acute pancreatitis (AP) and its complication liver injury. Transgelin-2 (TAGLN2), an actin-binding protein involved in inflammatory response, has been reported to be highly expressed in AP. However, the role of TAGLN2 in AP-induced liver injury remains unclear. Mice were treated with cerulein to construct the AP model in vivo, while Kupffer cells were stimulated with lipopolysaccharide (LPS) to mimic in vitro model. A series of in vitro and in vivo experiments were performed to investigate the role and mechanism of TAGLN2 in AP-induced liver injury. Cerulein administration induced pathological injury of the pancreatic and liver tissues, along with elevated levels of amylase, lipase, alanine aminotransferase (ALT), and aspartate transaminase (AST). TAGLN2 was significantly elevated at both the transcriptional and translational levels in the hepatocytes and Kupffer cells of AP mice. Knockout of TAGLN2 alleviated liver injury by reducing inflammatory cytokine levels, pyroptosis-related protein expression, and liver dysfunction markers. The relative levels of inflammatory factors, the expressions of pyroptosis-related proteins, and the pyroptosis rate were increased in LPS-induced Kupffer cells in an in vitro model, whereas TAGLN2 knockdown reversed these changes. Mechanistically, TAGLN2 promoted activation of the ANXA2/NF-κB axis in Kupffer cells, contributing to the inflammatory response. TAGLN2 exacerbates AP-induced liver injury by enhancing hepatocyte pyroptosis through Kupffer cell-mediated inflammatory activation of the ANXA2/NF-κB axis. Targeting TAGLN2 may offer a potential therapeutic strategy for mitigating liver injury in AP.

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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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