-
Views
-
Cite
Cite
C. Hill, A. Flyvbjerg, H. Grønbæk, J. Petrik, D. J. Hill, C. R. Thomas, M. C. Sheppard, A. Logan, The Renal Expression of Transforming Growth Factor-β Isoforms and Their Receptors in Acute and Chronic Experimental Diabetes in Rats, Endocrinology, Volume 141, Issue 3, March 2000, Pages 1196–1208, https://doi.org/10.1210/endo.141.3.7359
Close - Share Icon Share
Abstract
Transforming growth factors-β (TGF-β) are fibrogenic factors that have been strongly implicated in the development of diabetic nephropathy. Our aim was to use two animal models [the streptozotocin (STZ)-induced diabetic rat and the genetically prone biobreeding (BB) rat] to fully characterize the responses of the renal TGF-β system in both short- and long-term diabetes. In this study changes in the entire renal TGF-β system, at both protein and messenger RNA (mRNA) levels, have been characterized using the techniques of immunocytochemistry, Western blotting, and ribonuclease protection assay. We also used Western blotting of pro-collagen-I C-peptide to demonstrate that the rate of fibrogenesis was highest over the first 2 weeks of diabetes. TGF-β1, TGF-β2, and receptor mRNA and protein were detected in the control nondiabetic kidney. It was found that dramatic and dynamic changes occur in all parts of the renal TGF-β axis in both models of experimental diabetes, but TGF-β2 and TGF-βRII proteins were the predominant responsive element, particularly during the acute phase of disease. For example, during the acute phase of disease (0–30 days), although renal TGF-β1 mRNA levels were elevated, no increases in the corresponding protein were detected in the kidney. By contrast, in the absence of changes in TGF-β2 mRNA levels, twice as much TGF-β2 protein was measured in the kidney by day 30 of STZ-induced diabetes compared with day 0 controls analyzed by Western blotting (P < 0.05), and the protein was localized both to the nuclei and cytoplasm of glomerular cells, analyzed by immunocytochemistry. In addition, three times as much TGF-βRII protein was found by day 90 of STZ-induced diabetes compared with day 0 controls, making this the most responsive receptor type. These results suggest that the entire TGF-β axis has a role in the etiology of kidney fibrosis and could be manipulated therapeutically to preserve kidney function.
