MiR‐9 promotes angiogenesis of endothelial progenitor cell to facilitate thrombi recanalization via targeting TRPM7 through PI3K/Akt/autophagy pathway

Abstract

Endothelial progenitor cells (EPCs) have emerged as a promising therapeutic choice for thrombi recanalization. However, this role of EPCs is confined by some detrimental factors. The aim of this study was to explore the role of the miR-9-5p in regulation of the proliferation, migration and angiogenesis of EPCs and the subsequent therapeutic role in thrombosis event. Wound healing, transwell assay, tube formation assay and in vivo angiogenesis assay were carried out to measure cell migration, invasion and angiogenic abilities, respectively. Western blot was performed to elucidate the relationship between miR-9-5p and TRPM7 in the autophagy pathway. It was found that miR-9-5p could promote migration, invasion and angiogenesis of EPCs by attenuating TRPM7 expression via activating PI3K/Akt/autophagy pathway. In conclusion, miR-9-5p, targets TRPM7 via the PI3K/Ak/autophagy pathway, thereby mediating cell proliferation, migration and angiogenesis in EPCs. Acting as a potential therapeutic target, miR-9-5p may play an important role in the prognosis of DVT.

Clarification of the Role of miR-9 in the Angiogenesis, Migration, and Autophagy of Endothelial Progenitor Cells Through RNA Sequence Analysis

“…However, the limited capacities of homing and angiogenesis of EPCs impair their therapeutic effects. Intriguingly, our previous study demonstrated that miR-9 prevents apoptosis but promotes proliferation, migration, and angiogenesis of EPCs by targeting TRPM7, which enhances recanalization following venous thrombosis 24 . Although we identified the PI3K/Akt/autophagy pathway to be involved in the process, the effects of miR-9 on mRNA expression profiles of EPCs remain unclear.…”

“…Autophagy has attracted attention as a potential therapeutic target for vascular disease, and the process plays an important role in vascular biology and homeostasis and is implicated in many physiological and pathological processes involving cell angiogenesis and migration 33 . Our previous studies have shown miR-9 to promote EPC migration, proliferation, and angiogenesis by regulating autophagy and MMP2 protein expression, thereby promoting thrombolysis and vascularization in DVT 24 . However, tissue inhibitor of matrix metalloproteinases (TIMPs), specific inhibitor of MMPs, had no significant differences in our RNAseq results.…”

“…These small RNAs play a major role in the regulation of cell migration, proliferation, apoptosis, and angiogenesis, which is essential for the development and progression of vascular disease 23 . Our previous studies have suggested that miR-9 plays a crucial role in regulating angiogenesis and migration of EPCs by targeting transient receptor potential melastatin 7 (TRPM7) through the AKT autophagy pathway, thereby promoting thrombolysis and recanalization following DVT 24 . However, the detailed mechanisms underlying regulation of miR-9 in EPCs are poorly understood.…”

MiR-9 Promotes Angiogenesis via Targeting on Sphingosine-1- Phosphate Receptor 1

“…The role of miR-9 in angiogenesis is a promising therapy for many diseases. MiR-9 could promote migration, invasion, and angiogenesis of endothelial progenitor cells via downregulating transient receptor potential melastatin 7 (TRPM7) and activating PI3K/Akt/autophagy pathway, which might facilitate thrombi recanalization in deep vein thrombosis ( Zhou et al, 2020 ). Translocation of miR-9 from bone marrow-derived mesenchymal stem cells into vascular ECs could induce angiogenesis via activating PI3K/AKT pathway to repair the severe acute pancreatitis ( Qian et al, 2018 ).…”

“…We recently demonstrated that miR-9 promotes angiogenesis via activating the autophagy pathway ( Zeng et al, 2019 ). MiR-9 also promotes the angiogenesis of endothelial progenitor cells via activating the autophagy pathway ( Zhou et al, 2020 ). However, the molecular mechanism involved in miR-9-induced angiogenesis in ECs has not been fully explored.…”