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- Title
Effect of insulin-like growth factor binding proteins on the response of proximal tubular cells to insulin-like growth factor-I.
- Authors
Yap, Jason; Tsao, Tanny; Fawcett, Janet; Fielder, Paul J.; Keller, Gilbert A.; Rabkin, Ralph
- Abstract
Effect of insulin-like growth factor binding proteins on the response of proximal tubular cells to insulin-like growth factor-I, The insulin-like growth factor binding proteins (IGFBP) are major modulators of insulin-like growth factor-1 (IGF-I) action, but relatively little is known about their production by kidney tubular cells or about their modulating effects on the action of IGF-I on these cells. In this study we demonstrated that rabbit proximal tubular cells express the genes for IGFBP-2, -4 and -5 and secrete 24 and 32 kDa size binding proteins. The rate of IGFBP production by these cells was regulated by several growth factors including hydrocortisone, which was potently stimulatory; and EGF, which was inhibitory, The overall effect of these kidney cell-secreted IGFBPs was to inhibit the mitogenic activity of IGF-I. Similarly, recombinant 1GFBP-1 the major circulating IGFBP that in kidney is produced close to the proximal tubules, also inhibited IGF-I stimulated DNA synthesis in cultured rabbit proximal tubular cells and in cultured opossum kidney (OK) cells, IGFBP-3 also inhibited basal DNA synthesis in OK cells in the absence of added IGF-I, suggesting that this IGFBP may have an IGF-I independent action. These findings highlight the important effect that IGFBPs have on the action of IGF-I on kidney cells and support the notion that the changes in IGFBPs observed in various renal diseases may contribute to the pathophysiology of these diseases.
- Subjects
GROWTH factors; PANCREATIC secretions; EPIDERMAL growth factor; CARRIER proteins; NUCLEIC acids; KIDNEY diseases
- Publication
Kidney International, 1997, Vol 52, Issue 5, p1216
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1997.446