Exosomes from linc00511-overexpressing ADSCs accelerates angiogenesis in diabetic foot ulcers healing by suppressing PAQR3-induced Twist1 degradation

Aims: We aim to investigate the role of ADSCs (Adipose-derived stem cells)-derived exosomes on regulating angiogenesis in diabetic foot ulcers healing. Methods: 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. Results: 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 BTRCmediated Twist1 ubiquitin degradation. Exosomes from linc00511-overexpressing ADSCs alleviated rat diabetic foot ulcers by inhibiting Twist1 ubiquitination to promote angiogenesis. Conclusion: Exosomes from linc00511-overexpressing ADSCs promotes diabetic foot ulcers healing by accelerating angiogenesis via suppressing PAQR3-induced Twist1 ubiquitin degradation. (c) 2021 Elsevier B.V. All rights reserved.