1. miR‐126‐3p is essential for CXCL12‐induced angiogenesis
- Author
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Laurent Metzinger, Meriem Naïm, Nathalie Charnaux, Naïma Zaïdi, Valérie Metzinger-Le Meuth, Vincent Assoun, Kevin Bassand, Amena Butt, Christelle Laguillier-Morizot, Hanna Hlawaty, Olivier Oudar, Nesrine Mouhoubi, Angela Sutton, Erwan Guyot, Oualid Haddad, Odile Sainte-Catherine, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), BASSAND, Kévin, CHU Amiens-Picardie, and DESSAIVRE, Louise
- Subjects
0301 basic medicine ,Chemokine ,Necrosis ,Angiogenesis ,[SDV]Life Sciences [q-bio] ,Stimulation ,chemokine CXCL12 ,angiogenesis ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,medicine ,biology ,Chemistry ,Original Articles ,Cell Biology ,Transfection ,miR-126 ,endothelial cells ,biological factors ,In vitro ,miR‐126 ,Cell biology ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,030220 oncology & carcinogenesis ,embryonic structures ,biology.protein ,Molecular Medicine ,Original Article ,biological phenomena, cell phenomena, and immunity ,medicine.symptom ,Ex vivo - Abstract
International audience; Atherosclerosis, in the ultimate stage of cardiovascular diseases, causes an obstruction of vessels leading to ischemia and finally to necrosis. To restore vascularization and tissue regeneration, stimulation of angiogenesis is necessary. Chemokines and microRNAs (miR) were studied as pro-angiogenic agents. We analysed the miR-126/CXCL12 axis and compared impacts of both miR-126-3p and miR-126-5p strands effects in CXCL12-induced angiogenesis. Indeed, the two strands of miR-126 were previously shown to be active but were never compared together in the same experimental conditions regarding their differential functions in angiogenesis. In this study, we analysed the 2D-angiogenesis and the migration assays in HUVEC in vitro and in rat's aortic rings ex vivo, both transfected with premiR-126-3p/-5p or antimiR-126-3p/-5p strands and stimulated with CXCL12. First, we showed that CXCL12 had pro-angiogenic effects in vitro and ex vivo associated with overexpression of miR-126-3p in HUVEC and rat's aortas. Second, we showed that 2D-angiogenesis and migration induced by CXCL12 was abolished in vitro and ex vivo after miR-126-3p inhibition. Finally, we observed that SPRED-1 (one of miR-126-3p targets) was inhibited after CXCL12 treatment in HUVEC leading to improvement of CXCL12 pro-angiogenic potential in vitro. Our results proved for the first time: 1-the role of CXCL12 in modulation of miR-126 expression; 2-the involvement of miR-126 in CXCL12 pro-angiogenic effects; 3-the involvement of SPRED-1 in angiogenesis induced by miR-126/CXCL12 axis.
- Published
- 2021