IGF-binding protein-4 expression and IGF-binding protein-4 protease activity are regulated coordinately in smooth muscle during postnatal developmentand after vascular injury
Ep. Smith et al., IGF-binding protein-4 expression and IGF-binding protein-4 protease activity are regulated coordinately in smooth muscle during postnatal developmentand after vascular injury, ENDOCRINOL, 142(10), 2001, pp. 4420-4427
Recent studies support a critical role for the paracrine IGF/IGF-binding pr
otein system in the regulation of vascular smooth muscle cell growth. In th
is study we have explored the hypothesis that the abundance of individual I
GF-binding proteins in smooth muscle is subject to regulation during postna
tal life and in response to injury. IGF-binding protein-2 was the predomina
nt binding protein secreted by neonatal rat vascular smooth muscle cells, w
hereas IGF-binding protein-4 was most prevalent in adult vascular smooth mu
scle cells coincident with increased IGF-binding protein-4 protease activit
y. After arterial injury, IGF-binding protein-4 mRNA increased, associated
with greater IGF-binding protein-4 proteolytic activity, resulting in stabl
e steady state levels of the IGF-binding protein-4 protein. Expression of p
regnancy-associated plasma protein A mRNA, recently identified as an IGF-bi
nding protein-4 protease, was expressed at higher levels in adult than neon
atal vascular smooth muscle cell lines, but did not change significantly af
ter arterial injury. The peak of immunoreactive pregnancy-associated plasma
protein A from hydrophobic interaction chromatography fractions of smooth
muscle cell-conditioned medium coincided, but did not fully overlap, with t
he fractions containing maximal IGF-binding protein-4 protease activity. In
conclusion, our data point to a developmental switch from IGF-binding prot
ein-2 to IGF-binding protein-4 in vascular smooth muscle cells postnatally.
Moreover, IGF-binding protein-4 expression is coregulated with IGF-binding
protein-4 protease activity, suggesting that biosynthesis and degradation
of this binding protein are coordinated events important for regulating bio
logical activity of IGF-1.