title: Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus.
abstract: Long noncoding RNAs (lncRNAs) have important roles in diverse biological processes. Our previous study has revealed that lncRNA-MALAT1 deregulation is implicated in the pathogenesis of diabetes-related microvascular disease, diabetic retinopathy (DR). However, the role of MALAT1 in retinal vasculature remodeling still remains elusive. Here we show that MALAT1 expression is significantly upregulated in the retinas of STZ-induced diabetic rats and db/db mice. MALAT1 knockdown could obviously ameliorate DR in vivo, as shown by pericyte loss, capillary degeneration, microvascular leakage, and retinal inflammation. Moreover, MALAT1 knockdown could regulate retinal endothelial cell proliferation, migration, and tube formation in vitro. The crosstalk between MALAT1 and p38 MAPK signaling pathway is involved in the regulation of endothelial cell function. MALAT1 upregulation represents a critical pathogenic mechanism for diabetes-induced microvascular dysfunction. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for diabetes-related microvascular complications.
authors.affiliation: 1] Eye Hospital, Nanjing Medical University, Nanjing, China [2] The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Liu
authors.affiliation: 1] Eye Hospital, Nanjing Medical University, Nanjing, China [2] The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Yao
authors.affiliation: Eye Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: X-M
authors.initials: XM
authors.lastname: Li
authors.affiliation: 1] Eye Hospital, Nanjing Medical University, Nanjing, China [2] The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Song
authors.affiliation: 1] Eye Hospital, Nanjing Medical University, Nanjing, China [2] The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: 1] Eye Hospital, Nanjing Medical University, Nanjing, China [2] The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Li
authors.affiliation: 1] Eye Hospital, Nanjing Medical University, Nanjing, China [2] The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: B
authors.initials: B
authors.lastname: Yan
authors.affiliation: 1] Eye Hospital, Nanjing Medical University, Nanjing, China [2] The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China [3] Institute of Integrated Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D055785:Gene Knockdown Techniques; D007249:Inflammation; D020935:MAP Kinase Signaling System; D051379:Mice; D018919:Neovascularization, Physiologic; D062085:RNA, Long Noncoding / Q000378:metabolism*; D051381:Rats; D012171:Retinal Vessels / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C000598685:MALAT1 long noncoding RNA, rat; C557040:Malat1 long non-coding RNA, mouse; D062085:RNA, Long Noncoding; D048051:p38 Mitogen-Activated Protein Kinases