INSULIN-LIKE GROWTH-FACTOR-I INDUCES MESANGIAL PROLIFERATION AND INCREASES MESSENGER-RNA AND SECRETION OF COLLAGEN

Insulin-like growth factor I (IGF-1) is a peptide growth factor that i s synthesized in cultured mesangial cells and induces hyperplasia. We tested whether incubation with IGF-1 at concentrations of 7 nM, 70 nM, and 350 nM stimulates mesangial cell extracellular matrix mRNA and pr otein levels, and whether it influences mesangial cell growth. Mesangi al cells incubated with IGF-I demonstrated a statistically significant increase in procollagen alpha 1(I) (100 +/- 13% vs. 147 +/- 12%, 154 +/- 10%, and 173 +/- 21%) and alpha 1(IV) (100 +/- 9% vs. 112 +/- 9%, 125 +/- 8%, and 172 +/- 28%) mRNA. Furthermore, IGF-1 also stimulated a statistically significant increment in alpha 1(IV) mRNA in isolated glomeruli when measured by Northern hybridization and corroborated by in situ hybridization experiments. In addition, mesangial cells incuba ted with IGF-1 induced a statistically significant increase in both se creted and cell associated type I (secreted: 100 +/- 5% vs. 127 +/- 9% , 148 +/- 5%, 178 +/- 11%; and cell-associated: 100 +/- 19 vs. 132 +/- 17%, 198 +/- 24%, and 314 +/- 17%) and type IV (secreted: 100 +/- 9% vs. 138 +/- 11%, 192 +/- 17%, 379 +/- 16%; and cell-associated: 100 +/ - 8% vs. 139 +/- 10%, 206 +/- 16%, 310 +/- 15%) collagen. Thus, mRNA a nd collagen levels increased in a dose dependent fashion after incubat ion with IGF-1. Furthermore, IGF-1 stimulated hyperplasia but not hype rtrophy in this in vitro system. These data suggest that IGF-1 may con tribute to glomerular sclerosis by increasing mesangial matrix product ion as well as proliferation.