SMAD3 and renal fibrosis: Because TGF-β/Smad3 signaling was highly activated in the diabetic kidney associated with a marked upregulation of CD32b and severe renal fibrosis in CRPtg-db/db mice (Figs 3, 4, 6 and Supplementary Fig. S3), we hypothesized that CRP may activate Smad3 via the CD32b-dependent mechanism, which was investigated in vitro in HK-2 tubular epithelial cells.