Protective effects of IFN-γ on the kidney of type- 2 diabetic KKAy mice

Development of novel therapeutic strategies that specifically target diabetic kidney disease (DKD) is urgently needed.

Male KKAy mice were divided randomly into three equal groups - KK, KI, and KF; Male C57BL/6 mice were the control group. All KKAy mice were fed a high-fat diet. From the 16th week, the KI group was given IFN-γ, and the KF group was assigned to be treated with fludarabine. C57BL/6 mice were always fed a normal mouse diet. Every 4 weeks, body weight, random blood sugar, urine albumin and urea of all mice were measured. At the 20th week, all mice were killed, renal tissue was obtained to observe the pathological manifestations and extract proteins, and transforming growth factor- beta1 (TGF-β1), collagen IV and Janus kinase 2/signal transducers and activators of transcription 1 (JAK2/STAT1) pathway proteins were measured by western blot.

The present study showed that all KKAy mice appeared obese and hyperglycaemic from 12 weeks old and exhibited an increased urine albumin-to-creatinine ratio (ACR) from 16 weeks old. At the 20th week, compared to the KK group, the KI group showed lower ACR, more overexpression of P-STAT1 and less expression of TGF-β1 and collagen IV proteins in renal tissue. The KI group mice showed less accumulation of glomerular mesangial matrix than those in the KK group.

Our results indicate that IFN-γ might activate STAT1 to suppress the overexpression of TGF-β1 and collagen IV proteins and attenuate the excessive accumulation of mesangial matrix under DKD conditions in KKAy mice.