IGFBP-3 mediates TGF-beta1-induced cell growth in human airway smooth muscle cells.
Both insulin-like growth factor binding protein-3 (IGFBP-3) and transforming growth factor-beta (TGF-beta) have been separately shown to have cell-specific growth-inhibiting or growth-potentiating effects. TGF-beta stimulates IGFBP-3 mRNA and peptide expression in several cell types, and TGF-beta-induced growth inhibition and apoptosis have been shown to be mediated through the induction of IGFBP-3. However, a link between the growth stimulatory effects of TGF-beta and IGFBP-3-induction has not been shown. In this study, we investigated the role of IGFBP-3 in mediating TGF-beta1-induced cell growth using human airway smooth muscle (ASM) cells as our model. TGF-beta1 (1 ng/ml) treatment induced a 10- to 20-fold increase in the levels of expression of IGFBP-3 mRNA and protein. Addition of either IGFBP-3 or TGF-beta1 to the growth medium resulted in an approximately twofold increase in cell proliferation. Coincubation of ASM cells with IGFBP-3 antisense (but not sense) oligomers as well as with an IGFBP-3 neutralizing antibody (but not with control IgG) blocked the growth induced by TGF-beta1 (P < 0.001). Several IGFBP-3-associated proteins were observed in ASM cell lysates, which may have a role in the cellular responses to IGFBP-3. These findings demonstrate that IGFBP-3 is capable of mediating the growth stimulatory effect of TGF-beta in ASM cells.
Cohen
P
P
Department of Pediatrics, Mattel Children's Hospital at University of California, Los Angeles, California 90095-1752, USA.
Rajah
R
R
Rosenbloom
J
J
Herrick
D J
DJ
D000293:Adolescent; D000328:Adult; D001980:Bronchi / Q000166:cytology* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta