Long Non-Coding RNA Malat1 Regulates Angiogenesis in Hindlimb Ischemia

• Published in: International journal of molecular sciences Vol. 19; no. 6; p. 1723
• Main Authors: Zhang, Xuejing, Tang, Xuelian, Hamblin, Milton H, Yin, Ke-Jie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.06.2018; MDPI
• Subjects: Adenocarcinoma; Angiogenesis; Animals; Blood flow; Blood vessels; Cell adhesion & migration; Cell Movement; Cell Proliferation; Deprivation; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Gastrocnemius muscle; Gene Deletion; Gene expression; Gene Silencing; Glucose; Growth factors; Hindlimb - blood supply; Hindlimb - pathology; hindlimb ischemia; Immunoprecipitation; Ischemia; Ischemia - genetics; long non-coding RNA; Lung cancer; Malat1; Metastases; Mice; Microvasculature; Microvessels - pathology; Molecular modelling; Muscle, Skeletal - blood supply; Muscles; Neovascularization, Physiologic - genetics; Non-coding RNA; Nucleic acids; Perfusion; Protein Binding; Regional Blood Flow; Reperfusion; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Skeletal muscle; Transcription; vascular endothelial cells; Vascular endothelial growth factor; Vascular endothelial growth factor receptor 2; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGFR2; VEGFR2; Malat1; long non-coding RNA; vascular endothelial cells; angiogenesis; hindlimb ischemia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19061723

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 ( ) as an oxygen-glucose deprivation (OGD)-responsive endothelial lncRNA. Here we reported that genetic deficiency of leads to reduced blood vessel formation and local blood flow perfusion in mouse hind limbs at one to four weeks after hindlimb ischemia. and vascular endothelial growth factor receptor 2 ( ) 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, 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 directly targets VEGFR2 to facilitate angiogenesis. The results suggest that regulates cell-autonomous angiogenesis through direct regulation of VEGFR2.