IGF-binding protein-4 expression and IGF-binding protein-4 protease activity are regulated coordinately in smooth muscle during postnatal development and after vascular injury.
Recent studies support a critical role for the paracrine IGF/IGF-binding protein system in the regulation of vascular smooth muscle cell growth. In this study we have explored the hypothesis that the abundance of individual IGF-binding proteins in smooth muscle is subject to regulation during postnatal life and in response to injury. IGF-binding protein-2 was the predominant binding protein secreted by neonatal rat vascular smooth muscle cells, whereas IGF-binding protein-4 was most prevalent in adult vascular smooth muscle cells coincident with increased IGF-binding protein-4 protease activity. After arterial injury, IGF-binding protein-4 mRNA increased, associated with greater IGF-binding protein-4 proteolytic activity, resulting in stable steady state levels of the IGF-binding protein-4 protein. Expression of pregnancy-associated plasma protein A mRNA, recently identified as an IGF-binding protein-4 protease, was expressed at higher levels in adult than neonatal vascular smooth muscle cell lines, but did not change significantly after 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 the fractions containing maximal IGF-binding protein-4 protease activity. In conclusion, our data point to a developmental switch from IGF-binding protein-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 biological activity of IGF-I.
Smith
E P
EP
Division of Endocrinology, University of Cincinnati College of Medicine, Ohio 45267-0547, USA.
Kamyar
A
A
Niu
W
W
Wang
J
J
Cercek
B
B
Chernausek
S D
SD
Fagin
J A
JA
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000502:physiology; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000502:physiology*; D008666:Metalloendopeptidases / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology*; D011266:Pregnancy-Associated Plasma Protein-A; D012333:RNA, Messenger / Q000502:physiology; D051381:Rats
D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D008666:Metalloendopeptidases; D011266:Pregnancy-Associated Plasma Protein-A