Role of transforming growth factor-beta(1) and -beta(2) in ddY mouse nephropathy

We investigated the glomerular distribution of transforming growth factor-beta (TGF-beta(1) and TGF-beta(2)) protein and the expression of its mRNA, and related factors, in ddY mice, aged 5 - 60 weeks, before and after the onset of nephropathy. TGF-beta(1) protein expression was observed from the age of 20 weeks onwards, peaking at 50 weeks, and then declining. Expression of TGF-beta(2) protein gradually increased from 5 to 60 weeks. TGF-beta(1) and TGF-beta(2) mRNA were both detected from 5 to 60 weeks. The mesangial matrix expansion index (MMEI) was significantly higher in mice with nephropathy than in those without nephropathy, as was the expression of TGF-beta(1) and TGF-beta(2) proteins (P < 0.05). TGF-beta(2) was significantly positively correlated with the MMEI (P < 0.05). Infiltration of CD68-positive monocytes/macrophages gradually increased until 60 weeks, and was significantly correlated with the expression of TGF-beta(1) (P < 0.05) and TGF-beta(2) (P < 0.01). These findings indicate that TGF-beta(1) and TGF-beta(2) were overexpressed in ddY mice with overt nephropathy compared with pre-nephropathic mice. TGF-beta(2) may be an important mediator of mesangial matrix expansion in ddY mouse nephropathy.