Characterization of type I IGF receptor and IGF-I mRNA expression in cultured human and bovine glomerular cells

Regul Pept. 1993 Oct 20;48(1-2):9-20. doi: 10.1016/0167-0115(93)90331-2.

Abstract

Glomerular hypertrophy is reported in several endocrine disorders such as acromegaly and diabetes mellitus, where abnormalities of growth hormone and insulin-like growth factor (IGF-I) have been reported. In the present report, we have cultured bovine and human glomerular endothelial cells, and bovine glomerular epithelial and mesangial cells, and characterized the expression of IGF-I mRNA and its receptor in these cells. High affinity, specific receptors for IGF-I were identified in all three types of cells by radioreceptor assays. Receptor number (Ro) derived by Scatchard analysis revealed an unusually high number of Type I IGF receptors, approx. 1.2 x 10(5) receptors/cell in glomerular endothelial cells. Affinity crosslinking studies and immunoprecipitation with antibodies against the Type I IGF receptor identified the alpha-subunit of the IGF-I receptor as having a molecular mass of 140 kDa. Biologically, IGF-I was more potent than insulin or IGF-II in stimulating DNA synthesis in glomerular endothelial cells. Northern blot analysis showed that glomerular and aortic endothelial cells expressed IGF-1 mRNA of 1.7 kb. In contrast, renal glomeruli showed several IGF-1 mRNAs of 7.5, 1.7 and 1.2 kb. Thus, the demonstration of both a prepondence of Type I IGF receptors coupled with the growth promoting effects of IGF-I in glomerular endothelial and epithelial cells, as well as the local production of IGF-I mRNA suggests that IGF-I serves an important role as an autocrine or paracrine regulator of the growth of renal glomeruli.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Blotting, Northern
  • Cattle
  • Cells, Cultured
  • DNA / biosynthesis
  • Endothelium / metabolism
  • Epithelium / metabolism
  • Glomerular Mesangium / metabolism
  • Humans
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor I / isolation & purification
  • Insulin-Like Growth Factor I / metabolism
  • Kidney Cortex / metabolism
  • Kidney Glomerulus / metabolism*
  • Kinetics
  • Molecular Weight
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism*
  • Receptor, IGF Type 1 / biosynthesis*
  • Receptor, IGF Type 1 / isolation & purification
  • Receptor, IGF Type 1 / metabolism
  • Thymidine / metabolism

Substances

  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • DNA
  • Receptor, IGF Type 1
  • Thymidine