PMID- 7691836
OWN - NLM
STAT- MEDLINE
DCOM- 19931105
LR  - 20111117
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 157
IP  - 1
DP  - 1993 Oct
TI  - Vascular smooth muscle cells synthesize two forms of insulin-like growth factor 
      binding proteins which are regulated differently by the insulin-like growth 
      factors.
PG  - 52-60
AB  - Vascular smooth muscle cells (SMC) synthesize insulin-like growth factor-I 
      (IGF-I), which is a mitogen for this cell type in vitro. Since IGF binding 
      proteins (IGFBP) modulate IGF bioactivity, we determined which IGFBPs were 
      secreted by porcine SMC. Porcine SMC secreted 34,000 and 24,000 M(r) forms of 
      IGFBPs which were identified as IGFBP-2 and IGFBP-4, respectively, by 
      immunoblotting. Northern blot analysis showed single transcripts of 1.6 kb and 
      2.4 kb for IGFBP-2 and IGFBP-4, respectively. Secretion of IGFBP-2 was not 
      regulated to a significant degree, with insulin, IGF-II, IGF-I, forskolin, and 
      dibutyryl cyclic adenosine monophosphate (cAMP) inducing minimal changes in 
      IGFBP-2 secretion of less than 30% by radioimmunoassay (RIA). Insulin increased 
      (2.8 +/- 0.1-fold) the abundance of IGFBP-4 protein in conditioned media (CM) and 
      increased IGFBP-4 mRNA levels. Growth factors for SMC such as platelet-derived 
      growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor 
      (EGF), and transforming growth factor beta-1 (TGF beta-1) were without effect on 
      either IGFBP-2 or -4. IGF-I treatment decreased the amount of IGFBP-4 present in 
      CM, but a corresponding decrease in IGFBP-4 mRNA levels was not observed. In 
      order to determine if IGFBP-4 could modulate IGF-I bioactivity, IGFBP-4 was added 
      to pSMCs with and without IGF-I. IGF-I alone (20 ng/ml) induced a 1.6 to 
      threefold increase in 3H-thymidine incorporation. Addition of IGFBP-4 (between 50 
      and 250 ng/ml) to cultures containing IGF-I (20 ng/ml) had no effect on DNA 
      synthesis compared to that observed with IGF-I alone, while 500 ng/ml 
      consistently caused a small decrease (15 +/- 5%; mean +/- SE). Immunoblotting of 
      the CM obtained at the end of the 3H-thymidine assay showed a loss of intact 
      IGFBP-4 in the cultures containing IGF-I. This corresponded with an increase in 
      the abundance of a 16,000 M(r) immunoreactive fragment that did not bind IGF-I. 
      Coincubation with insulin had no effect on the amount of IGFBP-4 that was 
      converted to fragment, suggesting that the reaction was dependent upon IGF-I 
      binding to IGFBP-4. In contrast, addition of IGFBP-4 (500 ng/ml) to human 
      fibroblast cultures with IGF-I (20 ng/ml) almost completely inhibited the 
      stimulatory effect of IGF-I on DNA synthesis and no increase in fragment was 
      detected in the CM. In summary, SMC secrete IGFBP-2 and IGFBP-4, both of which 
      have been shown to regulate IGF-mediated DNA synthesis.(ABSTRACT TRUNCATED AT 400 
      WORDS)
FAU - Cohick, W S
AU  - Cohick WS
AD  - Department of Medicine, University of North Carolina School of Medicine, Chapel 
      Hill 27599.
FAU - Gockerman, A
AU  - Gockerman A
FAU - Clemmons, D R
AU  - Clemmons DR
LA  - eng
GR  - HL26309/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Carrier Proteins)
RN  - 0 (Insulin)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 2)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 4)
RN  - 0 (RNA, Messenger)
RN  - 0 (Somatomedins)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Carrier Proteins/*biosynthesis/chemistry/genetics
MH  - Cells, Cultured
MH  - Immunoblotting
MH  - Insulin/pharmacology
MH  - Insulin-Like Growth Factor Binding Protein 2
MH  - Insulin-Like Growth Factor Binding Protein 4
MH  - Molecular Weight
MH  - Muscle, Smooth, Vascular/cytology/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Radioimmunoassay
MH  - Somatomedins/*pharmacology
EDAT- 1993/10/01 00:00
MHDA- 1993/10/01 00:01
CRDT- 1993/10/01 00:00
PHST- 1993/10/01 00:00 [pubmed]
PHST- 1993/10/01 00:01 [medline]
PHST- 1993/10/01 00:00 [entrez]
AID - 10.1002/jcp.1041570107 [doi]
PST - ppublish
SO  - J Cell Physiol. 1993 Oct;157(1):52-60. doi: 10.1002/jcp.1041570107.