Stimulation of collagen formation by insulin and insulin-like growth factor I in cultures of human lung fibroblasts.
We examined the effects of insulin and insulin-like growth factor I (IGF-I) on the production of collagen by cultures of human embryonic lung fibroblasts. Insulin at 20 ng/ml increased collagen accumulation by 58% and total protein formation by 18%. At 2 micrograms/ml, insulin increased collagen production by 2- to 3-fold and total protein production by 2-fold. The mRNA levels for alpha 1(I) and alpha 1(III) collagen chains were elevated by insulin compared with untreated control values. IGF-I at 10 ng/ml increased collagen production 2-fold. IGF-I at 100 ng/ml maximally increased collagen production 3-fold. A specific antibody to the IGF-I receptor (alpha IR-3) caused a concentration-related decline in insulin-induced collagen formation. The addition of antibody at 1 micrograms/ml, resulted in 80% inhibition of insulin-induced collagen accumulation. Higher levels of antibody were required to inhibit IGF-I mediated collagen formation. The presence of antibody (alpha IR-3) also blocked fibroblast proliferation stimulated by epidermal growth factor plus insulin. These data show that insulin-induced collagen formation is mediated primarily through an interaction with the IGF-I receptor. The modulation of extracellular matrix production by insulin may influence the repair of tissue injury and the development of the accelerated atherosclerosis that accompanies the diabetic state in humans.
Goldstein
R H
RH
Pulmonary Center, Boston University Medical Center, Massachusetts.
Poliks
C F
CF
Pilch
P F
PF
Smith
B D
BD
Fine
A
A
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D013002:Somatomedins / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D007328:Insulin; D013002:Somatomedins; D012313:RNA; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline; D013936:Thymidine