TUG1 enhances high glucose-impaired endothelial progenitor cell function via miR-29c-3p/PDGF-BB/Wnt signaling
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RESEARCH
Open Access
TUG1 enhances high glucose-impaired endothelial progenitor cell function via miR-29c-3p/PDGF-BB/Wnt signaling Yang Li1,2†, Kangkang Zhi3†, Shilong Han1,2, Xue Li1,2, Maoquan Li1,2, Weishuai Lian1,2*, Haijun Zhang1,2* and Xiaoping Zhang1,2*
Abstract Background: Diabetes is associated with the dysfunction of endothelial progenitor cells (EPCs), characterized as impaired angiogenesis, a phenomenon thought to be involved in the development of diabetic foot. lncRNA plays an essential role in microvascular dysfunction and signaling pathways in patients with diabetes. lncRNA taurine upregulated gene 1 (TUG1) participates in angiogenesis in various cells. However, the mechanisms of TUG1 activity in EPCs have not been elucidated. Methods: We isolated and then characterized EPCs from the peripheral blood of mice using immunofluorescence and flow cytometry. Western blot detected the wnt/β-catenin pathway in high glucose-treated EPCs. Bioinformatics analysis predicted a putative binding site for TUG1 on miR-29c-3p. The interactions among TUG1, platelet-derived growth factor-BB (PDGF-BB), and miR-29c-3p were analyzed by luciferase assays. In vivo, diabetic mouse ischemic limb was treated with normal saline or TUG1 overexpression lentiviruses. Results: We found that EPC migration, invasion, and tube formation declined after treatment with high glucose, but improved with TUG1 overexpression. Mechanically, wnt/β-catenin pathway and autophagy were involved in the function of TUG1 overexpression in high glucose-treated EPCs. Moreover, TUG1 regulates the PDGF-BB/wnt pathway and function of high glucose-treated EPCs via miR-29c-3p. In vivo, injection of TUG1 lentivirus in a diabetic mouse ischemic limb model stimulated angiogenesis. Conclusions: Our findings suggest that TUG1 restores high glucose-treated EPC function by regulating miR-29c-3p/ PDGF-BB/Wnt signaling. Keywords: lncRNA taurine upregulated gene 1, Platelet-derived growth factor-BB, Endothelial progenitor cells, Diabetes, Angiogenesis
* Correspondence: [email protected]; [email protected]; [email protected] † Yang Li and Kangkang Zhi are co-first authors. 1 Department of Interventional & Vascular Surgery, Tenth People’s Hospital of Tongji University, Shanghai 200072, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted us
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