title: MicroRNA-146a and its adapter proteins are affected by diabetes in rat's heart.
abstract: OBJECTIVE
  This study was conducted to explore whether microRNA-146a and its adapter proteins (TNF-α receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1)) are affected by diabetes in the rat heart.
  
  
  METHODS
  Twelve male Sprague-Dawley rats were randomized into control and diabetic groups (n = 6). Streptozotocin-nicotinamide experimental model was used to induce type 2 diabetes. The gene expression of MicroRNA-146a, nuclear factor-κB (NF-κB), IRAK1 and TRAF6, as well as NF-κB activity, IRAK1 and TRAF6 protein levels were measured. Moreover, NF-κB activity was measured in response to miR-146a mimic transfection (20 nmol) in human umbilical vein endothelial cells (HUVECs) under hyperglycemic condition (25 mM D-glucose for 24 h).
  
  
  RESULTS
  The expression of MicroRNA-146a was increased in the heart tissue, 2 months after diabetes induction and in HUVECs. Also, the mRNA and protein levels of NF-κB, IRAK1 and TRAF6 were increased in the heart of diabetic rats. Moreover, transfection of miR-146a mimic prevented from a significant increase of NF-κB activity in hyperglycemic HUVECs.
  
  
  CONCLUSIONS
  Presumably, a defect in the regulation of IRAK1 and TRAF6 can weaken miR-146a regulatory effect and provides a situation for sustained activation of NF-κB and its targets to promote cardiac cells toward abnormalities (Fig. 3, Ref. 28).
authors.forename: E
authors.initials: E
authors.lastname: Eftekhar
authors.forename: M
authors.initials: M
authors.lastname: Doustaki Zaboli
authors.forename: M
authors.initials: M
authors.lastname: Katebi
authors.forename: F Ghadiri
authors.initials: FG
authors.lastname: Soufi
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*
chemical_list: C554180:MIRN146 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases; D005947:Glucose
keywords: IRAK1; NF-κB; TRAF6.; diabetes; heart; microRNA-146a