Renal Expression and Usefulness of TGF-β-inducible Gene-h3 in Human Type II Diabetic Nephropathy -Immunohistochemical Analysis-

Background: Activation of transforming growth factor-β (TGF-β) system has been implicated in the pathological change of diabetic nephropathy such as renal hypertrophy and accumulation of extracellular matrix. In tissues, TGF-β is secreted as a biologically inactive complex requiring in vivo activation. Thus, increased TGF-β1 mRNA or protein may not necessarily reflect parallel changes in TGF-β1 biologic activity. TGF-β1 inducible gene-h3 (βig-h3) is a novel gene uniquely up-regulated by active TGF-β1. Methods: For evaluating the βig-h3 protein expression in human diabetic nephropathy, we examed the expression of βig-h3 protein, TGF-β1, TGF-β type II receptor (TRII) and Smad protein intranuclear translocation by immunohistochemistry in human diabetic nephropathy tissues (n=11) and normal renal tissue (n=3). Results: The βig-h3 protein was expressed in diabetic tubular epithelium (diabetes vs. normal 7/11 vs. 0/3) and diabetic glomerulus (diabetes vs. normal 5/11 vs. 0/3). The tubular expression was stronger than the interstitial expression. The TGF-β1 was expressed in diabetic tubular epithelium (diabetes vs. normal 1/11 vs. 0/3) and diabetic glomerulus (diabetes vs. normal 3/11 vs. 0/3). The TGF-β type II was expressed more in diabetic glomerulus (diabetes vs normal 6/11 vs. 1/3). But in the tubule, the expression didn’t show any significant difference. The number of intranuclear translocation of Smad protein in glomerulus (diabetes vs normal 49.1±0.3 vs. 40.1±0.8) was increased in diabetes, but the tubular manifestation was not significant. Conclusion: We propose that TGF-β system mediates human diabetic nephropathy through βig- h3 protein expression. The βig-h3 protein expression could be a useful marker expecting of disease activity and progress.ope