MiR‐181a/b‐5p regulates human umbilical vein endothelial cell angiogenesis by targeting PDGFRA. (27th December 2019)

• Record Type: Journal Article
• Authors: Sun, Tingting; Yin, Linan; Kuang, Hongyu
• Is Part Of: Cell biochemistry and function. Volume 38:Number 2(2020)
• Page Start: 222
• Page End: 230
• Publication Date: 2019-12-27
• Subjects: angiogenesis -- HUVECs -- miR‐181a‐5p -- miR‐181b‐5p -- PDGFRA; Cytochemistry -- Periodicals; Cell metabolism -- Periodicals; Biochemistry -- Periodicals; Cytology -- Periodicals; 572
• DOI: 10.1002/cbf.3472
• Languages: English
• ISSNs: 0263-6484

Abstract

Abstract : Type 2 diabetes mellitus (T2DM) is a growing burden in low‐and middle‐income countries. Changing lifestyles and lack of physical activity are some of the reasons contributing to this epidemic increase. Co‐morbidities associated with T2DM are largely due to the complications which arise as a consequence of endothelial dysfunction. Platelet derived growth factor‐alpha (PDGFRA) is a protein responsible for cell proliferation, angiogenesis, migration and invasion. Increased levels of PDGFRA have been reported in T2DM. This study assessed the epigenetic regulation of PDGFRA through microRNAs ( miR‐181a / b‐5p ).Using a bioinformatics‐based approach, we assessed the binding of miR‐181a / b‐5p to PDGFRA. Experimentally, this binding was confirmed using a dual luciferase reporter assay. Further, we overexpressed miR‐181a / b‐5p in Human umbilical vein endothelial cells (HUVECs) and the influence of over‐expression on cell proliferation, migration and angiogenesis was assessed using in‐vitro approaches. The influence of miR‐181a / b‐5p over expression on cellular apoptosis was ascertained using a TUNEL assay with concomitant changes being observed in the levels of Bcl‐2 and cleaved Caspase‐3.In HUVECs, PDGFRA is a direct target for miR‐181a / b‐5p . Over expression of miR‐181a / b‐5p decreased cellular proliferation, migration, invasion, and tube formation—a surrogate marker for angiogenesis. miR‐181a / b‐5p may be used as a therapeutic intervention to restrict uncontrolled levels of PDGFRA and thereby rescue the phenotypes of increased cell proliferation, migration, invasion and tube formation. miR‐181a /b negatively regulates PDGFRA levels. Significance of the study : T2DM and its associated complications emerge from endothelial dysfunction. The associated phenotypes are regulated by a number of proteins, one such member being, PDGFRA. PDGFRA is in turn regulated by miR‐181a / b‐5p . Complementation with miR‐181a / b‐5p resulted in reversion of phenotypes. Thus, miR‐181a / b‐5p ‐mediated suppression of PDGFRA may be used as a therapeutic intervention in the management of type 2 diabetes.