Characterization of type I IGF receptor and IGF-I mRNA expression in cultured human and bovine glomerular cells.
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.
Ohashi
H
H
Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215.
Rosen
K M
KM
Smith
F E
FE
Villa-Komaroff
L
L
Nayak
R C
RC
King
G L
GL
D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004727:Endothelium / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005920:Glomerular Mesangium / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D007700:Kinetics; D008970:Molecular Weight; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D004247:DNA; D017526:Receptor, IGF Type 1; D013936:Thymidine