Connective tissue growth factor (CTGF) stimulates vascular smooth muscle cell growth and migration in vitro

doi:10.1078/0171-9335-00122

European Journal of Cell Biology

Volume 79, Issue 12, December 2000, Pages 915-923

https://doi.org/10.1078/0171-9335-00122 Get rights and content

Summary

Connective tissue growth factor (CTGF) was first identified as a 38-kDa cysteine-rich protein which can be specifically induced by TGF-beta and was recently found to be expressed abundantly in atherosclerotic lesions, but only marginally in normal vascular tissues. It was hypothesized that CTGF is one of the factors involved in the development of atherosclerotic lesions. In this study, we investigated the functions of CTGF protein in regulating the growth and migration of vascular smooth muscle cells (VSMC) and found that by overexpressing CTGF in VSMC, proliferation and migration rates were significantly increased. The accelerated growth and migration can be reversed by an anti-CTGF antibody. In addition, overexpression of CTGF also promotes VSMC to express more extracellular matrix protein collagen I and fibronectin. Our results indicate that CTGF is a growth factor for VSMC and it may play a similar role in promoting VSMC proliferation, migration, and formation of extracellular matrix, in vivo.

References (31)

K. Frazier et al.
Stimulation of fibroblast cell growth, Matrix production, and granulation tissue formation by connective tissue growth factor
J. Invest. Dermatol.
(1996)
M.L. Kireeva et al.
Cyr61 and Fisp12 are both ECM Associated signaling molecules: activities, metabolism, and localization during development
Exp Cell Res.
(1997)
D.C. MacLeod et al.
Proliferation and extracellular matrix synthesis of smooth muscle Cells cultured from human coronary atherosclerotic and restenotic Lesions
J. Am. Coll. Cardio.
(1994)
A.M. Babic et al.
Fisp12/mouse connective Tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo
Mol. Cell. Biol.
(1999)
D.K. Ball et al.
Characteriztion of 16- to 20-Kilodalton (kDa) connective tissue growth factors (CTGFs) and demonstration of proteolytic activity for 38-kDa CTGF in pig uterine luminal flushings
Biol. Reprod.
(1998)
E.J. Battegay et al.
TGF-beta induces bimodal proliferation of connective Tissue cells via complex control of an autocrine PDGF loop
Cell
(1990)
M. Boes et al.
Connective tissue growth factor (IGFBP-rP2) expression and regulation in cultured bovine endothelial cells
Endocrinology
(1999)
R.M. Bohmer et al.
Cytoskeletal integrity is required throughout the mitogen stimulation phase of The cell cycle and mediates the anchorage-dependent expression of cyclin D1
Mol. Biol. Cell
(1996)
D.M. Bradham et al.
Connective tissue growth factor: A cysteine-rich mitogen secreted by Human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10
J. Cell Biol.
(1991)
D.R. Brigstock
The connective tissue growth factor/Cysteine- Rich 61/nephroblastoma over expressed (CCN) family
Endocr. Rev.
(1999)

W.S. Cohick et al.

Regulation of Insulin-like growth factor (IGF) binding protein-2 synthesis and Degradation by platelet-derived growth factor and the IGFs is Enhanced by serum deprivation in vascular smooth muscle cells

J. Cell. Physiol.

(1995)

M.G. Davies et al.

Pathobiology of intimal hyperplasia

Br. J. Surg.

(1994)

G.R. Grotendorst

Connective tissue growth factor: a mediator Of TGF-beta action on fibroblasts

Cytokine Growth Factor Rev.

(1995)

Y. Hashimoto et al.

Expression of the Elm1 Gene, a novel gene of the CCN (connective tissue growth factor, cyr61/cef10, and neuroblastoma overexpressed gene) family, suppresses in vivo tumor growth and metastasis of K-1735 murine melanoma cells

J. Exp. Med.

(1998)

K. Hishikawa et al.

Overexpression of connective tissue growth factor gene induces apoptosis in human aortic smooth muscle cells

Circulation

(2000)

Cited by (120)

Effects of direct high sodium exposure at endothelial cell migration
2019, Biochemical and Biophysical Research Communications
The present study aimed to test the hypothesis that high sodium affects the migratory phenotype of endothelial cells (EC) and investigates mechanisms involved independently of hemodynamic factors. Cell migration was evaluated by Wound-Healing at conditions: High Sodium (HS; 160 mM) and Control (CT; 140 mM). O₂⁻ production was evaluated by DHE. NADPH oxidase activity was determined by chemiluminescence assay. Expression of adhesion molecules was analyzed by RT-PCR. Shear Stress was performed using a rhythmic shake. Nitric oxide production was measured by Griess reaction. HS-induced impairment in EC migration while both Candesartan and DPI prevented it. HS increased NADPH oxidase activity, which was blocked by Candesartan. Also, HS increased O₂⁻ production that was inhibited by Candesartan. HS decreased adhesion molecules expression via ROS (Integrin Alpha 5, Integrin Beta 1, Integrin Beta 3, VE-Cadherin and PECAM) and via AT1R (PECAM). The nitric oxide production induced by shear stress was decreased after EC exposure to HS while both Candesartan and DPI prevented it. Conclusion: This study demonstrated that HS reduced EC migration by AT1R and ROS derived from NADPH Oxidase and mitochondria. The HS reduction in adhesion molecules expression modulated by ROS and AT1R may help to explain the impairment in migration capacity. Also, HS affected EC functionality by reducing their nitric oxide production in response to shear stress.
Downregulation of miR-18a induces CTGF and promotes proliferation and migration of sodium hyaluronate treated human corneal epithelial cells
2016, Gene
Properly controlled corneal epithelial wound healing is critical for health of cornea, which involves cell proliferation, migration, anchoring and differentiation. Sodium hyaluronate (SH) has been proven to exert beneficial pharmacological effect on corneal wound healing, though the underlying mechanism remained open to investigation. MicroRNAs (miRNAs) are small single-stranded RNAs that could bind to 3′UTR of mRNAs of target genes. The multi-target regulation of miRNAs may favor treatment of corneal wound given the complicated processes implicated in the healing process, which has inspired initiatives to develop miRNA therapy in corneal wound healing. In this light, we used miRNAs profiling to detect whether miRNAs are also implicated in the mechanism underlying the stimulatory effect of SH on corneal epithelial wound healing. We found miR-18a was most susceptible to SH treatment, the target prediction of which were enriched in a bunch of pathways implicated in corneal wound healing. Connective tissue growth factor (CTGF) was found to be overrepresented in most significant enriched pathways and was experimentally confirmed as a bona fide target of miR-18a, which modulated cell migration and proliferation of human corneal epithelial cells.
The Inhibitory Effect of Connective Tissue Growth Factor Antibody on Postoperative Fibrosis in a Rabbit Model of Trabeculectomy
2022, Journal of Ophthalmic and Vision Research
Myometrial progesterone receptor determines a transcription program for uterine remodeling and contractions during pregnancy
2022, PNAS Nexus
Old blood from heterochronic parabionts accelerates vascular aging in young mice: transcriptomic signature of pathologic smooth muscle remodeling
2022, GeroScience
Connective-Tissue Growth Factor Contributes to TGF-b1-induced Lung Fibrosis
2022, American Journal of Respiratory Cell and Molecular Biology

View all citing articles on Scopus

View full text

Connective tissue growth factor (CTGF) stimulates vascular smooth muscle cell growth and migration in vitro

Summary

J. Invest. Dermatol.

Exp Cell Res.

J. Am. Coll. Cardio.

Fisp12/mouse connective Tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo

Mol. Cell. Biol.

Characteriztion of 16- to 20-Kilodalton (kDa) connective tissue growth factors (CTGFs) and demonstration of proteolytic activity for 38-kDa CTGF in pig uterine luminal flushings

Biol. Reprod.

TGF-beta induces bimodal proliferation of connective Tissue cells via complex control of an autocrine PDGF loop

Cell

Connective tissue growth factor (IGFBP-rP2) expression and regulation in cultured bovine endothelial cells

Endocrinology

Cytoskeletal integrity is required throughout the mitogen stimulation phase of The cell cycle and mediates the anchorage-dependent expression of cyclin D1

Mol. Biol. Cell

Connective tissue growth factor: A cysteine-rich mitogen secreted by Human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10

J. Cell Biol.

The connective tissue growth factor/Cysteine- Rich 61/nephroblastoma over expressed (CCN) family

Endocr. Rev.