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1-induced cell growth in human airway
smooth muscle cells
1 Department of Pediatrics, Mattel Children's Hospital at University of California, Los Angeles, California 90095-1752; and 2 Department of Anatomy, University of Pennsylvania, Children's Hospital, Philadelphia, Pennsylvania 19104
Both insulin-like growth factor binding protein-3
(IGFBP-3) and transforming growth factor-
(TGF-
) have been
separately shown to have cell-specific growth-inhibiting or
growth-potentiating effects. TGF-
stimulates IGFBP-3 mRNA and
peptide expression in several cell types, and TGF-
-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-
and IGFBP-3-induction has not been shown. In this
study, we investigated the role of IGFBP-3 in mediating
TGF-
1-induced cell growth using human airway smooth muscle (ASM)
cells as our model. TGF-
1 (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-
1 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-
1 (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-
in ASM cells.
insulin-like growth factor binding protein; cell proliferation; receptor; transforming growth factor.
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