PMID- 12831056
OWN - NLM
STAT- MEDLINE
DCOM- 20030825
LR  - 20220224
IS  - 0969-6970 (Print)
IS  - 0969-6970 (Linking)
VI  - 5
IP  - 3
DP  - 2002
TI  - Regulation of angiogenesis and endothelial cell function by connective tissue 
      growth factor (CTGF) and cysteine-rich 61 (CYR61).
PG  - 153-65
AB  - Connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61) are 
      prototypical members of the CCN family which also contains nephroblastoma 
      overexpressed (NOV) and Wnt-induced secreted proteins-1, -2 and -3 (WISP-1, -2, 
      -3). These proteins function as extracellular matrix (ECM)-associated signaling 
      molecules that contain structural modules allowing them to bind directly with 
      other moieties in the pericellular environment. Although multiple target cell 
      types have been identified for CCN proteins, there is strong evidence supporting 
      a role for CTGF and CYR61 in the regulation of endothelial cell function and 
      angiogenesis. Both CTGF and CYR61 can promote endothelial cell growth, migration, 
      adhesion and survival in vitro and at least some of these effects are mediated 
      through cell surface integrins. Both proteins are transcriptionally activated in 
      endothelial cells in response to basic fibroblast growth factor (bFGF) or 
      vascular endothelial growth factor (VEGF), and endothelial cell proliferation and 
      migration in vitro is reduced by antagonists of CTGF production or action. The 
      expression pattern of CTGF and CYR61 in endothelial cells of vessels in situ 
      supports a role for these molecules in normal endothelial homeostasis, as well as 
      participating in the angiogenic process during embryonic development, 
      placentation, tumor formation, fibrosis, and wound healing. CTGF or CYR61 
      knockout mice exhibit vascular defects during embryogenesis and fetal 
      development. Both CTGF and CYR61 are intrinsically active in in vivo asssays for 
      angiogenic activity. However, they can also regulate the production and/or 
      activity of other angiogenic molecules (e.g. bFGF, VEGF) as well molecules that 
      affect the integrity or stability of the ECM (e.g. collagen, matrix 
      metalloproteases (MMPs), tissue inhibitors of MMPs (TIMPs)). Therefore, through 
      their paracrine action as products of cells such as fibroblasts or smooth muscle 
      cells or through their autocrine action as products of endothelial cells, CTGF 
      and CYR61 participate in a variety of direct and indirect mechanisms by which 
      angiogenesis is regulated at multiple control points.
FAU - Brigstock, David R
AU  - Brigstock DR
AD  - Department of Surgery, The Ohio State University, Columbus, Ohio, USA. 
      brigstod@pediatrics.ohio-state.edu
LA  - eng
GR  - R01 AA12817/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Angiogenesis
JT  - Angiogenesis
JID - 9814575
RN  - 0 (CCN1 protein, human)
RN  - 0 (CCN2 protein, human)
RN  - 0 (CCN2 protein, mouse)
RN  - 0 (CCN3 protein, human)
RN  - 0 (Ccn3 protein, mouse)
RN  - 0 (Cysteine-Rich Protein 61)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Insulin-Like Growth Factor Binding Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lymphokines)
RN  - 0 (Nephroblastoma Overexpressed Protein)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Connective Tissue Growth Factor
MH  - Cysteine-Rich Protein 61
MH  - Endothelial Growth Factors/pharmacology
MH  - Endothelium, Vascular/*physiology
MH  - Extracellular Matrix/physiology
MH  - Fibroblast Growth Factor 2/pharmacology
MH  - Humans
MH  - Immediate-Early Proteins/drug effects/genetics/*physiology
MH  - Insulin-Like Growth Factor Binding Proteins/drug effects/genetics/*physiology
MH  - Intercellular Signaling Peptides and Proteins/genetics/pharmacology/*physiology
MH  - Lymphokines/pharmacology
MH  - Molecular Sequence Data
MH  - Neovascularization, Pathologic/*physiopathology
MH  - Neovascularization, Physiologic/*physiology
MH  - Nephroblastoma Overexpressed Protein
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction/physiology
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2003/07/02 05:00
MHDA- 2003/08/26 05:00
CRDT- 2003/07/02 05:00
PHST- 2003/07/02 05:00 [pubmed]
PHST- 2003/08/26 05:00 [medline]
PHST- 2003/07/02 05:00 [entrez]
AID - 10.1023/a:1023823803510 [doi]
PST - ppublish
SO  - Angiogenesis. 2002;5(3):153-65. doi: 10.1023/a:1023823803510.