IDDF2018-ABS-0230 Transglutaminase 2 modulates inflammation-associated angiogenesis via VEGFR2 pathway in crohn’s disease

Abstract

Background Angiogenesis is a vital component of the pathogenesis of inflammatory bowel disease(IBD). Vascular endothelial growth factor A(VEGF-A) and its receptors VEGFR2 are the pivotal component of angiogenesis in IBD. Recent studies suggest that transglutaminase 2 regulates angiogenesis in cancer and physiological conditions through VEGFR2 pathway. However, whether transglutaminase 2 are involved in this process of IBD remains elusive. Methods We use real-time PCR and Western blotting to validate the expression of TGM2 in CD patients‘ biopsy samples and TNBS-induced murine colitis. Furthermore, we use immunohistochemistry and immunofluorescence of surgical specimen and TNBS/DSS-induced murine colitis section to investigate the location of TGM2 in CD. To investigate the role of TGM2 in CD, human intestinal microvascular endothelial cells(HIMEC) and mouse intestinal microvascular endothelial cells(MIMEC) was treated with inflammatory cytokines. Finally, TNBS murine colitis model was treated with IL-9 neutralising antibody and weight loss, intestine length, as well as microvessel density, was evaluated after treatment. Results We found that the TGM2 was up-regulated in colonic mucosa of CD patients and TNBS-induced colitis. In addition, TGM2 expression mainly locates in microvessel. (figure 1) Furthermore, after treating with IL-9, TGM2 and VEGFR2 were significantly upgraded in HIMEC and MIMEC. In contrary, weight loss, intestine length, as well as microvessel density in TNBS murine colitis model, was significantly improved after treating with IL-9 neutralising antibody. Conclusions Our findings provide new evidence that TGM2 plays an important role in angiogenesis in CD, thus TGM2 may represent a novel therapeutic target for IBD.