Long Non-Coding RNA Malat1 Regulates Angiogenesis in Hindlimb Ischemia
AbstractAngiogenesis is a complex process that depends on the delicate regulation of gene expression. Dysregulation of transcription during angiogenesis often leads to various human diseases. Emerging evidence has recently begun to show that long non-coding RNAs (lncRNAs) may mediate angiogenesis in both physiological and pathological conditions; concurrently, underlying molecular mechanisms are largely unexplored. Previously, our lab identified metastasis associates lung adenocarcinoma transcript 1 (Malat1) as an oxygen-glucose deprivation (OGD)-responsive endothelial lncRNA. Here we reported that genetic deficiency of Malat1 leads to reduced blood vessel formation and local blood flow perfusion in mouse hind limbs at one to four weeks after hindlimb ischemia. Malat1 and vascular endothelial growth factor receptor 2 (VEGFR2) levels were found to be increased in both cultured mouse primary skeletal muscle microvascular endothelial cells (SMMECs) after 16 h OGD followed by 24 h reperfusion and in mouse gastrocnemius muscle that underwent hindlimb ischemia followed by 28 days of reperfusion. Moreover, Malat1 silencing by locked nucleic acid (LNA)-GapmeRs significantly reduced tube formation, cell migration, and cell proliferation in SMMEC cultures. Mechanistically, RNA subcellular isolation and RNA-immunoprecipitation experiments demonstrate that Malat1 directly targets VEGFR2 to facilitate angiogenesis. The results suggest that Malat1 regulates cell-autonomous angiogenesis through direct regulation of VEGFR2. View Full-Text
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Zhang, X.; Tang, X.; Hamblin, M.H.; Yin, K.-J. Long Non-Coding RNA Malat1 Regulates Angiogenesis in Hindlimb Ischemia. Int. J. Mol. Sci. 2018, 19, 1723.
Zhang X, Tang X, Hamblin MH, Yin K-J. Long Non-Coding RNA Malat1 Regulates Angiogenesis in Hindlimb Ischemia. International Journal of Molecular Sciences. 2018; 19(6):1723.Chicago/Turabian Style
Zhang, Xuejing; Tang, Xuelian; Hamblin, Milton H.; Yin, Ke-Jie. 2018. "Long Non-Coding RNA Malat1 Regulates Angiogenesis in Hindlimb Ischemia." Int. J. Mol. Sci. 19, no. 6: 1723.
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