Modulation of glomerular proteoglycans by insulin-like growth factor-1

Kidney Int. 1992 May;41(5):1262-73. doi: 10.1038/ki.1992.188.

Abstract

Effect of insulin-like growth factor-1 (IGF) on the synthesis of glomerular proteoglycans (PGs) in an ex vivo recirculating organ perfusion system was investigated. Kidneys were perfused with a medium (approximately 80 ml) containing [35S]-sulfate (250 microCi/ml) and IGF (62.5 to 625 ng/ml). After radiolabeling, a small cortical piece was saved for tissue autoradiography, and the remaining kidney and the perfusion medium were utilized for biochemical studies. The glomeruli were isolated; their PGs extracted and characterized. A two- to threefold increase of the total radioactivities in tissue and media fractions was observed with the exposure to IGF. By Sepharose CL-6B chromatography, the tissue PGs eluted as two peaks (A and B) with Kav = 0.24 and 0.48, and the majority of the radioactivity was confined to peak A. This peak contained intact PGs while peak B included glycosaminoglycan (GAG) chains. Elution profiles of the glomerular PGs were similar in the control and IGF groups. However, there was a disproportionate increase of chondroitin/dermatan sulfate in the IGF group. The media fractions also had two peaks, and most of the radioactivity was associated with peak B containing GAG chains. A remarkable accentuation of peak B along with significant increase in the chondroitin/dermatan sulfate were observed in the IGF group. By DEAE-Sephacel chromatography, the PGs/GAGs of IGF group eluted at a relatively lower salt concentration as compared to the control. Autoradiography revealed a relatively high concentration of radioactivity over the mesangium as compared to the other cell types of the glomerulus. [35S]-methionine studies revealed a generalized increase of protein synthesis in the IGF group, but comparatively much less than that of PGs/GAGs. These results indicate that IGF enhances the biosynthesis of PGs/GAGs by various cell types of the renal glomerulus, especially that of the mesangial cell, as reflected by the selective increase of chondroitin/dermatan sulfate.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoradiography
  • Chondroitin Sulfates / biosynthesis
  • Dermatan Sulfate / biosynthesis
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / metabolism
  • In Vitro Techniques
  • Insulin-Like Growth Factor I / pharmacology*
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / drug effects*
  • Kidney Glomerulus / metabolism
  • Male
  • Methionine / metabolism
  • Perfusion
  • Proteoglycans / biosynthesis*
  • Rats
  • Rats, Inbred Strains
  • Tissue Distribution

Substances

  • Proteoglycans
  • Dermatan Sulfate
  • Insulin-Like Growth Factor I
  • Chondroitin Sulfates
  • Methionine