Renal expression of transforming growth factor-β inducible gene-h3 (βig-h3) in normal and diabetic rats

Abstract

Background. Transforming growth factor-β (TGF-β) has been implicated in the pathogenesis of a number of kidney diseases characterized by glomerulosclerosis and tubulointerstitial fibrosis. TGF-β is secreted in a latent form requiring extracellular modification to become biologically active. TGF-β inducible gene-h3 (βig-h3) is a recently identified TGF-β- induced gene product. The present study sought to examine βig-h3 expression in normal and diabetic rats. Methods. βig-h3, TGF-β1 and α1 (IV) collagen gene expression were assessed by Northern blot analysis and in situ hybridization in 20 Sprague- Dawley rats, randomly assigned to receive streptozotocin (diabetic, N = 11) or citrate buffer alone (control, N = 9) and sacrificed eight months later. The effect of exogenous TGF-β1 on βig- h3 expression was also assessed in cultured proximal tubular cells. Results. In situ hybridization localized βig-h3 gene expression to the juxtaglomerular apparatus and the pars recta (S3 segment) of proximal tubules in both control and diabetic animals. Kidney TGF-β1, βig-h3 and α1 (IV) collagen mRNA from diabetic rats were increased two- to threefold compared with controls (P < 0.01). There was a significant correlation between TGF- β1 and βig-h3 gene expression in kidneys from diabetic rats (r = 0.73, P = 0.01). In addition, βig-h3 mRNA increased in response to exogenous TGF-β1 in a dose-dependent fashion in cultured proximal tubular cells. Conclusion. These findings support the hypothesis that biologically active TGF-β plays a pathogenetic role in diabetic kidney disease and suggest that βig-h3 may be a useful index of TGF-β1 bioactivity in the kidney.