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Int. J. Mol. Sci. 2018, 19(6), 1723; https://doi.org/10.3390/ijms19061723

Long Non-Coding RNA Malat1 Regulates Angiogenesis in Hindlimb Ischemia

1
Pittsburgh Institute of Brain Disorders & Recovery, Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
2
Department of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue SL83, New Orleans, LA 70112, USA
*
Author to whom correspondence should be addressed.
Received: 3 May 2018 / Revised: 28 May 2018 / Accepted: 5 June 2018 / Published: 11 June 2018
(This article belongs to the Collection Regulation by Non-Coding RNAs)
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Abstract

Angiogenesis 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
Keywords: long non-coding RNA; Malat1; angiogenesis; vascular endothelial cells; VEGFR2; hindlimb ischemia long non-coding RNA; Malat1; angiogenesis; vascular endothelial cells; VEGFR2; hindlimb ischemia
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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.

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