Figure 6.

rAAV-esRAGE treated TLR2^−/− diabetic kidney displayed a further protection against the progression of DN. (a,b) TLR2^−/−, TLR4^−/− or RAGE^−/− mice treated with either rAAV-HSA or rAAV-esRAGE exhibited less albuminuria compared to WT DN + HSA group, whilst no further protection was observed in diabetic knockout mice treated with esRAGE compared to those treated with HSA. (c–i) WT diabetic mice treated with rAAV-HSA developed significant renal pathology, including glomerular hypertrophy and hypercellularity, podocyte loss, mesangial expansion, interstitial fibrosis and macrophage accumulation, all of which were attenuated in WT DN + esRAGE mice. TLR2^−/− and TLR4^−/− diabetic mice treated with rAAV-HSA were partially protected against these diabetic kidney injuries (c–i), which is consistent with our previous studies. Treatment with rAAV-esRAGE provided further protection against kidney damage including glomerular hypertrophy (c) and hypercellularity (d), mesangial cells expansion (g), interstitial fibrosis (h) and macrophage accumulation (i) in TLR2^−/− mice, but not in TLR4^−/− diabetic mice (c,d,g–i). Both TLR2^−/− and TLR4^−/− diabetic mice treated with rAAV-esRAGE exhibited further protection against podocyte injury (e). Additional protection against podocin depletion was evident in rAAV-esRAGE TLR4^−/− diabetic mice (f). Data are presented as mean ± SD; *p < 0.05, **p < 0.01, ***p < 0.001.