Importantly, the pharmaceutic inhibition of ERK/p38 MAPKs or over-expression of Smad7 prevents AGEs-induced collagen production, suggesting the critical role of RAGE-ERK/p38 MAKPs-Smad crosstalk pathway in AGEs-induced fibrogenesis in DN [39,41] (Figure 1). The gene discussed is SMAD7; the disease is liver dysplastic nodule.