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.