Hormones – Cytokines – Signaling
Kidney International (1998) 54, 1052–1062; doi:10.1046/j.1523-1755.1998.00081.x
Renal expression of transforming growth factor-
inducible gene-h3 (ig-h3) in normal and diabetic rats1
Richard E Gilbert, Jennifer L Wilkinson-Berka, David W Johnson, Alison Cox, Tina Soulis, Leonard L Wu, Darren J Kelly, George Jerums, Carol A Pollock and Mark E Cooper
University of Melbourne Department of Medicine, Austin and Repatriation Medical Centre Heidelberg, Victoria, University of Sydney Department of Medicine, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
Correspondence: Dr Richard Gilbert, MB, BS, Ph.D., Department of Medicine, Austin and Repatriation Medical Centre, Repatriation Campus, Building 24, Waterdale Road, West Heidelberg 3081, Australia. E-mail: gilbert@austin.unimelb.edu.au
1See Editorial by Border and Noble, p. 1390.
Received 18 August 1997; Revised 23 April 1998; Accepted 30 April 1998.
Abstract
Renal expression of transforming growth factor-
inducible gene-h3 (ig-h3) in normal and diabetic rats.
Background
Transforming growth factor-
(TGF-) has been implicated in the pathogenesis of a number of kidney diseases characterized by glomerulosclerosis and tubulointerstitial fibrosis. TGF- is secreted in a latent form requiring extracellular modification to become biologically active. TGF- inducible gene-h3 (ig-h3) is a recently identified TGF--induced gene product. The present study sought to examine ig-h3 expression in normal and diabetic rats.
Methods
ig-h3, TGF-1 and 
1 (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-1 on ig-h3 expression was also assessed in cultured proximal tubular cells.
Results
In situ hybridization localized ig-h3 gene expression to the juxtaglomerular apparatus and the pars recta (S3 segment) of proximal tubules in both control and diabetic animals. Kidney TGF-1, ig-h3 and 1 (IV) collagen mRNA from diabetic rats were increased two- to threefold compared with controls (P < 0.01). There was a significant correlation between TGF-1 and ig-h3 gene expression in kidneys from diabetic rats (r = 0.73, P = 0.01). In addition, ig-h3 mRNA increased in response to exogenous TGF-1 in a dose-dependent fashion in cultured proximal tubular cells.
Conclusion
These findings support the hypothesis that biologically active TGF- plays a pathogenetic role in diabetic kidney disease and suggest that ig-h3 may be a useful index of TGF-1 bioactivity in the kidney.
Keywords:
transforming growth factor--inducible gene-h3, TGF-, diabetes, juxtaglomerular apparatus, proximal tubule, pars recta
Abbreviations:
1-col, 1-collagen; ig-h3, transforming growth factor- inducible gene-h3; DAB, diaminobenzidine tetrahydrochloride; EGF, epidermal growth factor; HGF, hepatocyte growth factor; HPLC, high performance liquid chromatography; IGF-1, insulin-like growth factor-1; JGA, juxtaglomerular apparatus; OSOM, outer stripe of the outer medulla; PTC, proximal tubular cells; STZ, streptozotocin; TGF, transforming growth factor
