title: Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells.
abstract: To examine whether the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is altered in the endothelial cells in response to glucose and the significance of such alteration. We incubated human umbilical vein endothelial cells with media containing various glucose levels. We found an increase in MALAT1 expression peaking after 12 hrs of incubation in high glucose. This increase was associated with parallel increase in serum amyloid antigen 3 (SAA3), an inflammatory ligand and target of MALAT1 and was further accompanied by increase in mRNAs and proteins of inflammatory mediators, tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Renal tissue from the diabetic animals showed similar changes. Such cellular alterations were prevented following MALAT1 specific siRNA transfection. Results of this study indicate that LncRNA MALAT1 regulates glucose-induced up-regulation of inflammatory mediators IL-6 and TNF-α through activation of SAA3. Identification of such novel mechanism may lead to the development of RNA-based therapeutics targeting MALAT1 for diabetes-induced micro and macro vascular complications.
authors: Department of Pathology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors: Prasanth
authors: P
authors: Puthanveetil
authors: Department of Pathology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors: Shali
authors: S
authors: Chen
authors: Department of Pathology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors: Biao
authors: B
authors: Feng
authors: Department of Pathology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors: Anirudh
authors: A
authors: Gautam
authors: Department of Pathology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors: Subrata
authors: S
authors: Chakrabarti
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D018836:Inflammation Mediators; D015850:Interleukin-6; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D017382:Reactive Oxygen Species; C489625:SAA3P protein, human; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose
keywords: IL6; MALAT1; TNFα; diabetes; endothelial cells; glucose; kidney