To determine the mechanism(s) of protection, we found that whilst deficiency of TLR2, TLR4 or RAGE afforded partial protection from development of DN, over-expression of esRAGE provided additional protection in TLR2<sup>-/-</sup>, modest protection against podocyte damage only in TLR4<sup>-/-</sup> and no protection in RAGE<sup>-/-</sup> diabetic mice, suggesting the protection provided by esRAGE was primarily through interruption of RAGE and TLR4 pathways.
The findings suggest that continuous infusion of RAGE-aptamer could attenuate the development and progression of experimental diabetic nephropathy by blocking the AGE-RAGE axis.
We also outline novel treatments targeting the AGE-RAGE axis and specific Nox isoforms, which hold great promise in attenuating the development of diabetes-associated atherosclerosis and diabetic nephropathy.
Our study indicated that the 2184A/G polymorphism in the RAGE gene was significantly associated with diabetic nephropathy in Chinese Han patients with type 2 diabetes.
After correction for multiple comparisons, only one SNP, in the gene encoding the receptor of advanced glycation end products, AGER 2184A/G (gene symbol formerly known as RAGE) showed a significant association with DN (p = 0.0006) in single-locus analysis.
RAGE- and TGF-beta receptor-mediated signals converge on STAT5 and p21waf to control cell-cycle progression of mesangial cells: a possible role in the development and progression of diabetic nephropathy.