| Autor: |
Xuerui Zhang, Lulu Song, Lin Li, Banghui Zhu, Lina Huo, Zhaoqing Hu, Xinran Wang, Jie Wang, Mengyue Gao, Jing Zhang, Zichun Hua |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2059-3635 |
| DOI: |
10.1038/s41392-021-00626-z |
| Popis: |
Abstract Inflammatory bowel disease (IBD) is a chronic and relapsing disorder for many people associated with poor health. Although there are some clinical drugs for IBD treatment, the development of effective therapeutics on IBD patients has always been necessary. Here, we show that externalized phosphatidylserine (PS) is observed on the surface of colonic capillaries. Annexin A5 (ANXA5) with high affinity for PS has a good targeting to the colon and effectively alleviates experimental colitis. In contrast, ANXA5 mutant (A5m) lacking the PS-binding ability, has no accumulation in the colon and no therapeutic effects on colitis. Mechanistic investigations indicate that ANXA5 reduces the inflammatory cell infiltration by inhibiting endothelial cell activation dependent on PS-binding ability. With the increasing of PS exposure on activated HUVECs (human umbilical vein endothelial cells), ANXA5 binding induces the internalization of TLR4 via PS-dependent endocytosis. We provide new insights on the molecular mechanism of ANXA5 for its anti-inflammatory effect. Our data suggest that PS-externalization is a potential target of ANXA5 aiming at targeted drug delivery (TDD) for IBD treatment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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