Department of Vascular Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China.
Department of Vascular Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China.
Diabetes Res Clin Pract. 2021 Oct;180:109032. doi: 10.1016/j.diabres.2021.109032. Epub 2021 Aug 28.
We aim to investigate the role of ADSCs (Adipose-derived stem cells)-derived exosomes on regulating angiogenesis in diabetic foot ulcers healing.
EPCs (endothelial progenitor cells) from human peripheral blood were applied as in vitro model of angiogenesis. Exosomes isolated from ADSCs culture medium were characterized by electron microscopy, size distribution and biomarker expression. Cell proliferation, migration, apoptosis and angiogenesis were detected by CCK-8 and EdU staining, wound healing, flow cytometry and tube formation assays, respectively. Rat diabetic foot model was further constructed for the evaluation of wound healing and histological alterations.
EPCs from diabetes showed suppressed proliferation, migration and angiogenesis and decreased Twist1 protein. Similarly, high glucose repressed the proliferation, migration and angiogenesis of EPCs, which also elevated PAQR3 and suppressed Twist1 expression. However, these impaired EPCs biological functions were recovered by the application of exosomes from linc00511-overexpressing ADSCs, along with increased Twist1 and decreased PAQR3. Mechanistically, PAQR3 overexpression reduced Twist1 protein level in EPCs by enhancing BTRC-mediated Twist1 ubiquitin degradation. Exosomes from linc00511-overexpressing ADSCs alleviated rat diabetic foot ulcers by inhibiting Twist1 ubiquitination to promote angiogenesis.
Exosomes from linc00511-overexpressing ADSCs promotes diabetic foot ulcers healing by accelerating angiogenesis via suppressing PAQR3-induced Twist1 ubiquitin degradation.
我们旨在研究脂肪干细胞（ADSCs）衍生的外泌体在调节糖尿病足溃疡愈合中的血管生成作用。
用人外周血中的内皮祖细胞（EPCs）作为体外血管生成模型。从 ADSC 培养基中分离的外泌体通过电子显微镜、大小分布和生物标志物表达进行表征。通过 CCK-8 和 EdU 染色检测细胞增殖、迁移、凋亡和血管生成，通过划痕愈合、流式细胞术和管形成测定分别检测细胞迁移和血管生成。进一步构建大鼠糖尿病足模型，评估伤口愈合和组织学改变。
糖尿病来源的 EPCs表现出增殖、迁移和血管生成受损，Twist1 蛋白减少。同样，高葡萄糖抑制 EPCs 的增殖、迁移和血管生成，同时也增加了 PAQR3 并抑制了 Twist1 表达。然而，过表达 linc00511 的 ADSC 衍生的外泌体的应用恢复了这些受损的 EPCs 生物学功能，同时增加了 Twist1 和减少了 PAQR3。机制上，PAQR3 通过增强 BTRC 介导的 Twist1 泛素降解来降低 EPCs 中的 Twist1 蛋白水平。过表达 linc00511 的 ADSC 衍生的外泌体通过抑制 Twist1 泛素化来促进血管生成，从而缓解大鼠糖尿病足溃疡。
过表达 linc00511 的 ADSC 衍生的外泌体通过抑制 PAQR3 诱导的 Twist1 泛素化降解，促进糖尿病足溃疡愈合，加速血管生成。
