Insulin-like growth factor I induces mesangial proliferation and increases mRNA and secretion of collagen.
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.
Feld
S M
SM
Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, USA.
Hirschberg
R
R
Artishevsky
A
A
Nast
C
C
Adler
S G
SG
D000818:Animals; D002250:Carbon Radioisotopes; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D006965:Hyperplasia / Q000378:metabolism; D006984:Hypertrophy / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000494:pharmacology*; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008297:Male; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D002250:Carbon Radioisotopes; D007797:Laminin; D011347:Procollagen; D012333:RNA, Messenger; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D007930:Leucine; D013936:Thymidine