{"title":"转谷氨酰胺酶2通过血管内皮生长因子受体2途径调节炎症性肠病中的炎症血管生成","authors":"Gaoshi Zhou, Mudan Zhang, Shuhui Zheng, Guang Yang, Li Li, Shanshan Huang, Zhirong Zeng, Rirong Chen, Shenghong Zhang, Minhu Chen","doi":"10.1016/j.jare.2025.07.002","DOIUrl":null,"url":null,"abstract":"<h3>Objectives</h3>Immune-driven inflammatory angiogenesis is a crucial component in the pathogenesis of inflammatory bowel disease (IBD). Nevertheless, the underlying mechanisms are still poorly understood. This study aims to investigate the role of Transglutaminase 2 (TGM2) in inflammatory angiogenesis in IBD and its potential as a therapeutic target and biomarker.<h3>Methods</h3>We performed an RNA-seq analysis integrated single-cell transcriptomic profiling on IBD biopsies to identify dysregulated genes. Additionally, we explored TGM2 contribution to angiogenesis and colitis under in vitro and in vivo conditions in <em>Tgm2</em> knockout mouse and human intestinal microvascular endothelial cells (HIMECs). Serum TGM2 levels were measured by Enzyme-Linked Immunosorbent Assay.<h3>Results</h3>TGM2 expression was significantly upregulated in intestinal endothelial cells of IBD patients and colitis models. <em>Tgm2</em> knockout and its inhibitor significantly attenuated intestinal colitis and angiogenesis in mice. In vitro, knockdown of TGM2 significantly suppressed tube formation, migration, and invasion of HIMECs. Mechanistically, inflammation-induced STAT1 activation promoted TGM2 expression, which subsequently interacted with vascular endothelial growth factor receptor 2 (VEGFR2) to drive its phosphorylation (Tyr1059, Tyr1214) and inflammatory angiogenesis. In patients of Crohn’s Disease, serum TGM2 concentrations exhibited high diagnostic accuracy (AUC = 0.862) for assessing endoscopic activity.<h3>Conclusion</h3>Our findings underscore the critical role of STAT1-TGM2-VEGFR2 axis in regulating angiogenesis during intestinal inflammation, suggesting that targeting TGM2 as a viable therapeutic candidate for vascular remodeling in chronic intestinal inflammation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 1","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Transglutaminase 2 modulates inflammatory angiogenesis via vascular endothelial growth factor receptor 2 pathway in inflammatory bowel disease\",\"authors\":\"Gaoshi Zhou, Mudan Zhang, Shuhui Zheng, Guang Yang, Li Li, Shanshan Huang, Zhirong Zeng, Rirong Chen, Shenghong Zhang, Minhu Chen\",\"doi\":\"10.1016/j.jare.2025.07.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3>Objectives</h3>Immune-driven inflammatory angiogenesis is a crucial component in the pathogenesis of inflammatory bowel disease (IBD). Nevertheless, the underlying mechanisms are still poorly understood. This study aims to investigate the role of Transglutaminase 2 (TGM2) in inflammatory angiogenesis in IBD and its potential as a therapeutic target and biomarker.<h3>Methods</h3>We performed an RNA-seq analysis integrated single-cell transcriptomic profiling on IBD biopsies to identify dysregulated genes. Additionally, we explored TGM2 contribution to angiogenesis and colitis under in vitro and in vivo conditions in <em>Tgm2</em> knockout mouse and human intestinal microvascular endothelial cells (HIMECs). Serum TGM2 levels were measured by Enzyme-Linked Immunosorbent Assay.<h3>Results</h3>TGM2 expression was significantly upregulated in intestinal endothelial cells of IBD patients and colitis models. <em>Tgm2</em> knockout and its inhibitor significantly attenuated intestinal colitis and angiogenesis in mice. In vitro, knockdown of TGM2 significantly suppressed tube formation, migration, and invasion of HIMECs. Mechanistically, inflammation-induced STAT1 activation promoted TGM2 expression, which subsequently interacted with vascular endothelial growth factor receptor 2 (VEGFR2) to drive its phosphorylation (Tyr1059, Tyr1214) and inflammatory angiogenesis. In patients of Crohn’s Disease, serum TGM2 concentrations exhibited high diagnostic accuracy (AUC = 0.862) for assessing endoscopic activity.<h3>Conclusion</h3>Our findings underscore the critical role of STAT1-TGM2-VEGFR2 axis in regulating angiogenesis during intestinal inflammation, suggesting that targeting TGM2 as a viable therapeutic candidate for vascular remodeling in chronic intestinal inflammation.\",\"PeriodicalId\":14952,\"journal\":{\"name\":\"Journal of Advanced Research\",\"volume\":\"9 1\",\"pages\":\"\"},\"PeriodicalIF\":13.0000,\"publicationDate\":\"2025-07-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Advanced Research\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jare.2025.07.002\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Advanced Research","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.jare.2025.07.002","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Transglutaminase 2 modulates inflammatory angiogenesis via vascular endothelial growth factor receptor 2 pathway in inflammatory bowel disease
Objectives
Immune-driven inflammatory angiogenesis is a crucial component in the pathogenesis of inflammatory bowel disease (IBD). Nevertheless, the underlying mechanisms are still poorly understood. This study aims to investigate the role of Transglutaminase 2 (TGM2) in inflammatory angiogenesis in IBD and its potential as a therapeutic target and biomarker.
Methods
We performed an RNA-seq analysis integrated single-cell transcriptomic profiling on IBD biopsies to identify dysregulated genes. Additionally, we explored TGM2 contribution to angiogenesis and colitis under in vitro and in vivo conditions in Tgm2 knockout mouse and human intestinal microvascular endothelial cells (HIMECs). Serum TGM2 levels were measured by Enzyme-Linked Immunosorbent Assay.
Results
TGM2 expression was significantly upregulated in intestinal endothelial cells of IBD patients and colitis models. Tgm2 knockout and its inhibitor significantly attenuated intestinal colitis and angiogenesis in mice. In vitro, knockdown of TGM2 significantly suppressed tube formation, migration, and invasion of HIMECs. Mechanistically, inflammation-induced STAT1 activation promoted TGM2 expression, which subsequently interacted with vascular endothelial growth factor receptor 2 (VEGFR2) to drive its phosphorylation (Tyr1059, Tyr1214) and inflammatory angiogenesis. In patients of Crohn’s Disease, serum TGM2 concentrations exhibited high diagnostic accuracy (AUC = 0.862) for assessing endoscopic activity.
Conclusion
Our findings underscore the critical role of STAT1-TGM2-VEGFR2 axis in regulating angiogenesis during intestinal inflammation, suggesting that targeting TGM2 as a viable therapeutic candidate for vascular remodeling in chronic intestinal inflammation.
期刊介绍:
Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences.
The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.