Upregulation of KIM-1 and Inflammatory Mediators is Associated with Kidney Tubular Injury in Diabetic Rat Model

Chronic diabetes mellitus (DM) leads to diabetic nephropathy (DN) that contributes to the Global Burden of Disease. Sprague Dawley male rats (3 months old, 200 grams) were divided into four groups: control (n=6) and DM groups that received an intraperitoneal injection of Streptozotocin (60 mg/kg BW) for 1 month (DM1, n=6), 2 months (DM2, n=6), and 4 months (DM4, n=6). The rats were sacrificed, and retro-orbital blood was withdrawn to assess creatinine serum levels. The kidneys were harvested to assess tubular injury by Periodic-Acid Schiff (PAS), kidney fibrosis by Sirius Red staining, and mRNA expression of KIM-1, E-Cadherin, and Vimentin by reverse transcriptase PCR (RT-PCR). Long-term diabetes mellitus enhanced creatinine serum level (p<0.001), tubular injury (p<0.05), and kidney fibrosis (p<0.001) in the DM2 and DM4 groups compared to the control group. mRNA expression of E-Cadherin significantly decreased in the DM4 group (p<0.05) while mRNA expression increased both in vimentin DM4 group (p<0.001) and KIM-1 DM4 group (p<0.05) compared to the control group. The inflammatory mediators consisting of NFκB, MCP1, and CD68 significantly increased in DM4 groups compared to the control group (p<0.05). Chronic diabetes mellitus elevates tubular injury and fibrosis and is associated with upregulation of KIM-1 mRNA expression.