ROLE OF TRANSFORMING GROWTH FACTOR-BETA(1) AND FACTOR-BETA(2) IN DDY MOUSE NEPHROPATHY

We investigated the glomerular distribution of transforming growth fac tor-beta (TGF-beta(1) and TGF-beta(2)) protein and the expression of i ts mRNA, and related factors, in ddY mice, aged 5 - 60 weeks, before a nd after the onset of nephropathy. TGF-beta(1) protein expression was observed from the age of 20 weeks onwards, peaking at 50 weeks, and th en declining. Expression of TGF-beta(2) protein gradually increased fr om 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 si gnificantly higher in mice with nephropathy than in those without neph ropathy, 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/macrophag es gradually increased until 60 weeks, and was significantly correlate d 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 ov erexpressed in ddY mice with overt nephropathy compared with pre-nephr opathic mice. TGF-beta(2) may be an important mediator of mesangial ma trix expansion in ddY mouse nephropathy.