Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney.
The present study was designed to evaluate whether microRNA-146a and its adapter proteins (TRAF6 and IRAK1) are involved in the pathogenesis of diabetes-induced kidney damage. Male Sprague-Dawley rats were divided into control and diabetic groups (n = 6 in each). Diabetes was induced by injection of streptozotocin (55 mg/kg; i.p.) in 12 h fasted rats. Diabetic kidney damage was diagnosed by renal hypertrophy, thickened glomerular basement membrane, widened filtration slits, mesangial expansion, as well as by elevated levels of blood urea and creatinine in diabetic rats 2 months after induction of diabetes. While the expression of NF-κB mRNA and miR-146a were increased in diabetic kidney compared to the sham controls (p < 0.01 for both comparisons), the mRNA levels of IRAK1 and TRAF6 did not statistically reduce. The NF-κB activity and the concentrations of TNF-α, IL-6 and IL-1β in the kidney of diabetic rats were higher than the kidney of controls (p < 0.05 for TNF-α and NF-κB; p < 0.01 for IL-6 and IL-1β). Our results indicate that the upregulation of miR-146a was not accompanied by downregulation of inflammatory mediators in diabetic kidney. It is possible that a defect in the miR-146a-mediated negative loop provides a situation for sustained activation of NF-κB and its targets to promote cells toward abnormalities.
Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Mohammad Reza
MR
Alipour
Amir Mahdi
AM
Khamaneh
Nasibeh
N
Yousefzadeh
Daryoush
D
Mohammad-nejad
Farhad Ghadiri
FG
Soufi
D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; C554180:MIRN146 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B