title: Long non-coding MIAT mediates high glucose-induced renal tubular epithelial injury.
abstract: OBJECTIVE
  Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs that take part in occurrence and development of diabetes complication via regulating gene expression. However, litter is known about lncRNAs in the setting of diabetes induced nephropathy. The aim of this study was to examine whether lncRNA-myocardial infarction-associated transcript (MIAT) is involved in diabetes induced renal tubules injury.
  
  
  METHODS
  Adult Wister rats were randomly assigned to receive intraperitoneal STZ (65 mg/kg) to induce diabetes. Rats treated with equal volume of citrate buffer were as control. Renal function was evaluated by analysis of serum creatinine and blood urea nitrogen (BUN) every four weeks after STZ administration. Also tubules of all rats were collected for determination of MIAT and Nrf2 level at the corresponding phase. The in vitro high glucose-triggered human renal tubular epithelial cell line (HK-2) was used to explore the mechanism underling MIAT regulated high glucose-induced tubular damage.
  
  
  RESULTS
  In diabetic rats, MIAT showed the lower level and its expression is negatively correlated with serum creatinine and BUN. Consistent with diabetic rat, exposed to high glucose, HK-2 cells expressed lower level of MIAT and Nrf2, and also showed reduction in cell viability. By pcDNA-MIAT plasmid transfection, we observed that MIAT overexpression reversed inhibitory action of Nrf2 expression by high glucose. Moreover, the data of RNA pull-down and RIP showed that MIAT controlled Nrf2 cellular through enhancing Nrf2 stability, which was confirmed by CHX and MG132 administration. Inhibitory effect of cell viability by silencing MIAT was also reversed by Nrf2 overexpression.
  
  
  CONCLUSIONS
  In summary, our data suggested that MIAT/Nrf2 served as an important signaling pathway for high glucose induced renal tubular epithelial injury.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: De-yu
authors.initials: DY
authors.lastname: Xu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Wen-gang
authors.initials: WG
authors.lastname: Sha
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China. Electronic address: guoyuan_l@163.com.
authors.forename: Guo-yuan
authors.initials: GY
authors.lastname: Lu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yin
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage*; D007684:Kidney Tubules / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*; D008297:Male; D062085:RNA, Long Noncoding / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C517383:Miat long non-coding RNA; D062085:RNA, Long Noncoding; D005947:Glucose
keywords: Cell viability; HK-2; Nrf2; Serum creatinine