期刊
MICROVASCULAR RESEARCH
卷 140, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2021.104306
关键词
Diabetic foot ulcer; Wound healing; Angiogenesis; miR-221-3p; HIPK2
资金
- National Natural Science Foundation of China [81970703, 81900750, 82170484]
- Subject Construction Project of Anhui Medical University [2021lcxk009]
The study found that miR-221-3p promotes the viability, migration, and tube formation of endothelial cells, and it achieves this by decreasing the expression of HIPK2. Injection of miR-221-3p in diabetic mice promotes wound healing and inhibits the expression of HIPK2.
Diabetic foot ulcer is a severe complication of diabetes and is prone to being a chronic non-healing wound. We previously demonstrated that endothelial progenitor cell-derived exosomes, which contain miR-221-3p, alleviate diabetic ulcers. Here, to explore the mechanisms underlying this wound healing, we investigated the potential angiogenic effects of miR-221-3p in vitro using cultured human umbilical vein endothelial cells (HUVECs) and in vivo using a streptozotocin-induced mouse model of diabetes. We found that miR-221-3p promoted HUVEC viability, migration, and capillary-like tube formation. HUVECs cultured in high glucose showed up-regulated expression of homeodomain-interacting protein kinase 2 (HIPK2), a predicted target of miR-221-3p that may decrease angiogenesis. Knockdown of HIPK2 enhanced high glucose-suppressed HUVEC viability, migration, and tube formation, counteracting the effects of high glucose. Using a dual luciferase reporter assay, we found that HIPK2 was indeed a direct target of miR-221-3p. Subcutaneous injection of miR-221-3p agomir into diabetic mice promoted wound healing and suppressed HIPK2 expression in wound margin tissue. These findings indicate that HIPK2, as a direct target of miR-221-3p, contributes to the regulatory role of miR-221-3p in diabetic wound healing and may be a novel therapeutic target for diabetic foot ulcer.
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