Insulin-like growth factor I induces mesangial proliferation and increases mRNA and secretion of collagen

Abstract

Insulin-like growth factor I (IGF-1) is a peptide growth factor that is 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 protein levels, and whether it influences mesangial cell growth. Mesangial cells incubated with IGF-1 demonstrated a statistically significant increase in procollagen α1(I) (100 ± 13% vs. 147 ± 12%, 154 ± 10%, and 173 ± 21%) and α1(IV) (100 ± 9% vs. 112 ± 9%, 125 ± 8%, and 172 ± 28%) mRNA. Furthermore, IGF-1 also stimulated a statistically significant increment in α1(IV) mRNA in isolated glommeruli when measured by Northern hybridization and corroborated by in situ hybridization experiments. In addition, mesangial cells incubated with IGF-1 induced a statistically significant increase in both secreted 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 and collagen levels increased in a dose dependent fashion after incubation with IGF-1. Furthermore, IGF-1 stimulated hyperplasia but not hypertrophy in this in vitro system. These data suggest that IGF-1 may contribute to glomerular sclerosis by increasing mesangial matrix production as well as proliferation.