Inhibition of diabetic nephropathy by a GH antagonist: A molecular analysis

Ciro Esposito, Zhi Hong Liu, Gary E. Striker, Carrie Phillips, Nian Yi Chen, Wen Y. Chen, John J. Kopchick, Liliane J. Striker

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43 Scopus citations

Abstract

Streptozotocin-treated C57B1/SJL mice developed glomerular hypertrophy and light microscopic lesions mimicking human diabetic glomerulosclerosis. In contrast, there were no glomerular hypertrophy and lesions in diabetic mice transgenic (TG) for a mutated growth hormone (bGH-G119K) that competes with native endogenous GH and results in dwarfism. We examined the molecular events underlying these findings. The non-transgenic (non-TG) diabetic mouse glomeruli had an increase in mRNA coding for αIIV collagen, laminin B1, TGF-β1, 72 kDa collagenase, and TIMP-3. In contrast, glomerular type IV collagen and laminin B1 mRNA levels were normal in diabetic TG dwarf mice. However, the 72 kDa gelatinase. TIMP-3, and TGF-β1 mRNAs were elevated in the diabetic dwarfs. Type IV collagen and laminin accumulated in the glomeruli of diabetic non-TG, but not of diabetic dwarf mice, by immunofluorescence microscopy, confirming the mRNA data. GH binding protein mRNA levels were comparable in glomeruli from dwarf and non-TG mice, both diabetic and non-diabetic. We did not detect GH receptor mRNA in glomeruli. These data suggest that diabetic glomerulosclerosis is associated with an increase in type IV collagen and laminin synthesis, and that these changes do not occur in mice transgenic for bGH119K, a functional antagonist of GH. The increase of 72 kDa gelatinase, TIMP-3, and TGF-β1 mRNAs, independent of GH, suggested that these changes induced by hyperglycemia were not sufficient for the induction of glomerulosclerosis.

Original languageEnglish (US)
Pages (from-to)506-514
Number of pages9
JournalKidney international
Volume50
Issue number2
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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    Esposito, C., Liu, Z. H., Striker, G. E., Phillips, C., Chen, N. Y., Chen, W. Y., Kopchick, J. J., & Striker, L. J. (1996). Inhibition of diabetic nephropathy by a GH antagonist: A molecular analysis. Kidney international, 50(2), 506-514. https://doi.org/10.1038/ki.1996.342