Up-regulated miR-204-5p promoted the migration, invasion, and angiogenesis of endothelial progenitor cells to enhance the thrombolysis of rats with deep venous thrombosis by targeting SPRED1

• Published in: Experimental cell research 2022-02, Vol.411 (1), p.112985-112985, Article 112985
• Main Authors: Ding, Mingchao, Chi, Guoqing, Li, Fang, Wang, Bin, Shao, Changgang, Song, Wenjie
• Format: Article
• Language: English
• Subjects: Adult; Animals; Apoptosis; Biomarkers - metabolism; Case-Control Studies; Cell Movement; Cell Proliferation; Cells, Cultured; Deep venous thrombosis; Endothelial progenitor cells; Endothelial Progenitor Cells - cytology; Endothelial Progenitor Cells - physiology; Female; Gene Expression Regulation; Humans; Male; MicroRNAs - genetics; miR-204-5p; Neovascularization, Physiologic; Prognosis; Rats; Rats, Sprague-Dawley; Repressor Proteins - antagonists & inhibitors; Repressor Proteins - genetics; Repressor Proteins - metabolism; Signal Transduction; SPRED1; Thrombolysis; Thrombolytic Therapy - methods; Transcriptional Activation; Up-Regulation; Venous Thrombosis - metabolism; Venous Thrombosis - pathology; Venous Thrombosis - therapy
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2021.112985

Deep venous thrombosis (DVT) endangers human health. Endothelial progenitor cells (EPCs) were proven to promote thrombolysis and miR-204-5p was discovered to be low-expressed in DVT patients. This study concentrated on exploring whether miR-204-5p had a regulatory effect on EPCs and DVT. Concretely, the expression of miR-204-5p in DVT patients’ blood was detected by qRT-PCR. The target of miR-204-5p was predicted by bioinformatics and verified by dual-luciferase reporter assay. After rat EPCs were isolated, identified, and transfected with miR-204-5p agomiR, antagomiR, or SPRED1 plasmids, the viability, migration, invasion, and tube formation of EPCs were detected by MTT, wound healing, Transwell, and tube formation assays, respectively. MiR-204-5p, SPRED1, p-PI3K, PI3K, p-AKT, AKT, VEGFA, and Ang1 expressions in EPCs were measured by qRT-PCR or Western blot. EPCs transfected with miR-204-5p overexpression lentivirus plasmid were injected into the DVT rat model. The histopathology of the thrombus and the homing of EPCs to thrombus in the DVT rats were observed by hematoxylin-eosin staining and confocal microscopy, respectively. We found that miR-204-5p was low-expressed in DVT patients and SPRED1 was a target gene of miR-204-5p. MiR-204-5p agomiR promoted the viability, migration, invasion, and tube formation of EPCs, the levels of VEGFA and Ang1 and the activation of PI3K/AKT pathway in EPCs, while miR-204-5p antagomiR and SPRED1 worked oppositely. SPRED1 reversed the effect of miR-204-5p agomiR on EPCs. Up-regulated miR-204-5p inhibited thrombosis and promoted EPCs homing to thrombus in DVT rats. Collectively, up-regulated miR-204-5p enhanced the angiogenesis of EPCs and thrombolysis in DVT rats by targeting SPRED1. •MiR-204-5p lowly expressed in patients with DVT.•MiR-204-5p regulated the migration, invasion, and tube formation of rats EPCs.•MiR-204-5p targeted SPRED1.•MiR-204-5p promoted the EPCs homing to thrombus and thrombolysis in DVT rats.