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Insulin-like growth factor I induces mesangial proliferation and increases mRNA and secretion of collagen
S M Feld1, R Hirschberg, A Artishevsky
1Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, USA.
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 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 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 +/- 19% 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.
Insights
Insulin-like growth factor I (IGF-1) significantly increases mesangial cell extracellular matrix production and proliferation. This suggests IGF-1 may play a role in glomerular sclerosis by promoting matrix accumulation and cell growth.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Biology
Background:
- Insulin-like growth factor I (IGF-1) is a peptide growth factor known to induce hyperplasia.
- Mesangial cells play a crucial role in kidney function and extracellular matrix regulation.
Purpose of the Study:
- To investigate the effect of IGF-1 on mesangial cell extracellular matrix mRNA and protein levels.
- To determine if IGF-1 influences mesangial cell growth (hyperplasia and hypertrophy).
Main Methods:
- Cultured human mesangial cells were incubated with varying concentrations of IGF-1 (7 nM, 70 nM, 350 nM).
- Procollagen alpha 1(I) and alpha 1(IV) mRNA levels were measured using Northern hybridization and in situ hybridization.
- Secreted and cell-associated type I and type IV collagen protein levels were quantified.
Main Results:
- IGF-1 significantly increased procollagen alpha 1(I) and alpha 1(IV) mRNA levels in a dose-dependent manner.
- IGF-1 also significantly stimulated the production of both type I and type IV collagen.
- The study observed a dose-dependent increase in mesangial cell hyperplasia but not hypertrophy.
Conclusions:
- IGF-1 stimulates extracellular matrix production and proliferation in mesangial cells.
- These findings suggest that IGF-1 may contribute to the development of glomerular sclerosis.
- Targeting IGF-1 signaling could be a potential therapeutic strategy for kidney diseases characterized by matrix accumulation.