Role of Transforming Growth Factor-β and -β in ddY Mous Nephropathy

Abstract

We investigated the glomerular distribution of transforming growth factor −β (TGF −β₁, and TGF −β₂) 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 −β₁ protein expression was observed from the age of 20 weeks onwards, peaking at 50 weeks, and then declining. Expression of TGF −β₂ protein gradually increased from 5 to 60 weeks. TGF −β₁ and TGF −β₂ 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 −β₁ and TGF −β₂ proteins (P < 0.05). TGF −β₂ 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 −β₁ (P < 0.05) and TGF −β₂ (P < 0.01). These findings indicate that TGF −β₁ and TGF −β₂ were overexpressed in ddY mice with overt nephropathy compared with pre-nephropathic mice. TGF −β₂ may be an important mediator of mesangial matrix expansion in ddY mouse nephropathy.