Analysis of physiological vascular network formation and maintenance in small intestinal villi

The intestine is the site of digestion and nutrient absorption and is constantly exposed to various stimuli from foreign substances. The intestinal capillary network plays an important role at the forefront of this. Nevertheless, it's still unclear how the vascular network is constructed during the construction of the capillary network accompanying the development of the mucosal layer and villi, including the small and large intestines, and what factors and cell interactions induce the construction of a precise vascular network during this process. Elucidating and understanding the process of physiological vascular network construction is important in terms of treatment strategies for various intestinal diseases, as well as avoiding side effects and improving treatment efficiency. In this study, we focused on the mechanism of vascular network construction in the physiological intestine and analyzed the role of RNF31 in maintaining the vascular network using conditional knockout mice in which RNF31 was specifically knocked out in vascular endothelial cells. Ring finger protein 31 (RNF31) is expressed systemically and plays a role in activating NF-kB and suppressing cell death. It has been reported to promote tumor malignancy in certain carcinomas. Additionally, RNF31 is known to be involved in vascular development, with its deficiency leading to impaired vascular development and embryonic lethality. Physiological vascular network construction in the small intestinal villi was observed from embryonic day 17.5 (E17.5) to 8 weeks of age (8w). As a result, it was confirmed that the vascular network is constructed according to a set rule along with the postnatal development of the villi. In addition, we found that EC-specific RNF31 knockout mice exhibited severe tissue destruction exclusively in the small intestine, and all died within three weeks. No significant differences were observed in the cecum, large intestine, or other organs compared to control mice. In this presentation, we will report on the trends in vascular morphology and changes in the expression of related factors during the construction and breakdown of the villi vascular network, as well as morphological changes focusing on leukocyte accumulation. Grant-in-Aid for Early-Career Scientists of Japan Society for the Promotion of Science This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.