Huigeng Zhao, Yalan Luo, Xi Chen, Ju Wu, Zizhao Zhu, Hailong Chen
{"title":"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。","authors":"Huigeng Zhao, Yalan Luo, Xi Chen, Ju Wu, Zizhao Zhu, Hailong Chen","doi":"10.2478/aite-2025-0014","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>in vivo</i>, while Kupffer cells were stimulated with lipopolysaccharide (LPS) to mimic <i>in vitro</i> model. A series of <i>in vitro</i> and <i>in vivo</i> 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 <i>in vitro</i> 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.</p>","PeriodicalId":8389,"journal":{"name":"Archivum Immunologiae et Therapiae Experimentalis","volume":"73 1","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"TAGLN2 Exacerbates Acute Pancreatitis-Induced Liver Injury by Increasing Hepatocyte Pyroptosis via Kupffer Cells-Mediated Inflammatory Response.\",\"authors\":\"Huigeng Zhao, Yalan Luo, Xi Chen, Ju Wu, Zizhao Zhu, Hailong Chen\",\"doi\":\"10.2478/aite-2025-0014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>in vivo</i>, while Kupffer cells were stimulated with lipopolysaccharide (LPS) to mimic <i>in vitro</i> model. A series of <i>in vitro</i> and <i>in vivo</i> 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 <i>in vitro</i> 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.</p>\",\"PeriodicalId\":8389,\"journal\":{\"name\":\"Archivum Immunologiae et Therapiae Experimentalis\",\"volume\":\"73 1\",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-06-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archivum Immunologiae et Therapiae Experimentalis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2478/aite-2025-0014\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archivum Immunologiae et Therapiae Experimentalis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2478/aite-2025-0014","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
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.
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.