ACTA1 and renal fibrosis: As shown in Figure 2, PAS-staining and immunohistochemistry demonstrated that pre-diabetic treatment with SIS3 at the dose of 2.5mg/kg/day protected against the development of T2DN by largely reducing the glomerular matrix expansion and progressive renal fibrosis such as extensive accumulation of collagen I, IV, FN, and α-SMA+ myofibroblasts (Figure 2A-F).