Dysregulation of kidney structural polysaccharides and miRNA-21/SIRT1/NF-κB axis of injury and fibrosis in thioacetamide-induced nephrotoxicity is protected by resveratrol

1. MicroRNA-21 (miRNA-21) expression is increased in patients with kidney disease, and polysaccharides provide the structural scaffolding of the glomerular and tubular basement membranes. 2. We investigated whether the induction of renal injury by the industrial toxic chemical thioacetamide (TAA) can dysregulate the kidney miRNA-21/SIRT1/NF-κB axis as well as the structural polysaccharide content of the kidney tissue, and whether treatment with the polyphenolic compound resveratrol can inhibit these adverse effects. 3. Kidney injury was induced in rats by TAA (200 mg/kg) injections. The protective group of rats was pre-treated with resveratrol (20 mg/kg) prior to kidney injury and subsequently kept on resveratrol until culled. 4. TAA intoxication caused a significant (p < 0.0001) modulation in kidney and blood levels of miRNA-21, the tissue renoprotective molecule SIRT1, NF-κB p65, kidney structural polysaccharides, the macrophage biomarker cluster of differentiation 68 (CD68), tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, hypernatremia, urea, and creatinine, as well as albuminuria that were significantly (p ≤ 0.0187) protected by resveratrol. Furthermore, a significant correlation between the miRNA-21/ SIRT1/NF-κB axis, structural polysaccharides, renal fibrosis, and renal injury biomarkers was observed. 5. These findings demonstrate an association between renal injury induced by TAA intoxication and the dysregulation of the kidney miRNA-21/SIRT1/NF-κB axis and polysaccharide levels while being protected by resveratrol.