Connective tissue growth factor mediates transforming growth factor β‐induced collagen synthesis: down‐regulation by cAMP

  title={Connective tissue growth factor mediates transforming growth factor $\beta$‐induced collagen synthesis: down‐regulation by cAMP},
  author={Matthew R. Duncan and Kendall S Frazier and Susan R Abramson and S Williams and Herbert Klapper and X Huang and Gary R. Grotendorst},
  journal={The FASEB Journal},
  pages={1774 - 1786}
Connective tissue growth factor (CTGF) is a cysteine‐rich peptide synthesized and secreted by fibroblastic cells after activation with transforming growth factor beta (TGF‐β) that acts as a downstream mediator of TGF‐β‐induced fibroblast proliferation. We performed in vitro and in vivo studies to determine whether CTGF is also essential for TGF‐β‐induced fibroblast collagen synthesis. In vitro studies with normal rat kidney (NRK) fibroblasts demonstrated CTGF potently induces collagen synthesis… 

Interleukin‐4 regulates connective tissue growth factor expression in human lung fibroblasts

Transforming growth factor‐β (TGF‐β) and interleukin‐4 (IL‐4) have fibrogenic properties and induce extracellular matrix production in a variety of lung diseases and regulation of CTGF expression by IL‐4 in human lung fibroblasts was examined.

Inhibition of connective tissue growth factor/CCN2 expression in human dermal fibroblasts by interleukin‐1α and β

These results add to the understanding of how the expression of CTGF in human dermal fibroblasts is regulated, which in turn may have implications for the pathogenesis of fibrotic conditions involving the skin.

cAMP Inhibits Transforming Growth Factor-β-Stimulated Collagen Synthesis via Inhibition of Extracellular Signal-Regulated Kinase 1/2 and Smad Signaling in Cardiac Fibroblasts

Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Cytokines such as transforming growth factor-β (TGF-β) play a

Connective tissue growth factor (CTGF/CCN2) is a downstream mediator for TGF‐β1‐induced extracellular matrix production in osteoblasts

It is demonstrated for the first time that CTGF is an essential downstream mediator for TGF‐β1‐induced ECM production and cell growth in osteoblasts, but these two growth factors function independently regarding their opposing effects on osteoblast proliferation.

Down‐regulation of connective tissue growth factor and type I collagen mRNA expression by connective tissue growth factor antisense oligonucleotide during experimental liver fibrosis

The results suggest that hepatic stellate cells can be targeted in vivo with oligonucleotides, and that reducing CTGF levels can lead to a decrease in fibrogenesis as shown by the reduction in type I collagen expression.

Connective tissue growth factor expression and induction by transforming growth factor-beta is abrogated by simvastatin via a Rho signaling mechanism.

It is shown that simvastatin through a Rho signaling mechanism in lung fibroblasts can modulate CTGF expression and interaction with TGF-beta, a finding further supported by transfection of dominant-negative and constitutively active RhoA constructs.

CTGF expression is induced by TGF- beta in cardiac fibroblasts and cardiac myocytes: a potential role in heart fibrosis.

It is proposed that CTGF is an important mediator of TGF- beta signaling in the heart and abnormal expression of this gene could be used as a diagnostic marker for cardiac fibrosis.

ALK-5 mediates endogenous and TGF-beta1-induced expression of connective tissue growth factor in embryonic lung.

It is demonstrated for the first time that TGF-beta1 induces CTGF expression in mouse embryonic lung explants, that CTGF inhibits branching morphogenesis, and that both endogenous and T GF- beta1-induced CTGFexpression are mediated by the TbetaRI/ALK-5-dependent Smad2 signaling pathway.

Hepatocyte growth factor counteracts transforming growth factor‐β1, through attenuation of connective tissue growth factor induction, and prevents renal fibrogenesis in 5/6 nephrectomized mice

HGF can block, at least partially, renal fibrogenesis promoted by TGF‐β1 in the remnant kidney, via attenuation of CTGF induction.

Inhibition of host connective tissue growth factor expression: a novel Trypanosoma cruzi‐mediated response

The novel finding that the intracellular pathogen Trypanosoma cruzi elicits immediate and sustained repression of basal CTGF expression in dermal fibroblasts, followed by down‐regulation of the extracellular matrix proteins, fibronectin, and collagen I α1 is presented.



Inhibition of TGF‐β‐stimulated CTGF gene expression and anchorage‐independent growth by cAMP identifies a CTGF‐dependent restriction point in the cell cycle

Kinetic studies of the induction of DNA synthesis by CTGF in cells arrested by cAMP indicate that the block occurs in very late G1, and studies in monolayer cultures suggest that the CTGF restriction point in the cell cycle is distinct from the adhesion‐dependent arrest point.

Transforming growth factor beta induces anchorage-independent growth of NRK fibroblasts via a connective tissue growth factor-dependent signaling pathway.

It is demonstrated that the TGF-beta stimulation of NRK fibroblast AIG is dependent on events induced via the synergistic action of CTGF-dependent andCTGF-independent signaling pathways.

Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor.

It is demonstrated that, like TGF-beta, CTGF can induce connective tissue cell proliferation and extracellular matrix synthesis.

Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair.

It is demonstrated that human foreskin fibroblasts produce high levels of CTGF mRNA and protein after activation with transforming growth factor beta (TGF-beta) but not other growth factors including PDGF, epidermal growth factor, and basic fibroblast growth factor.

Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor.

The observations suggest that TGF‐beta exerts a selective effect on extracellular matrix deposition by modulating the action of other growth factors on metalloproteinase and TIMP expression.

Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.

  • A. RobertsM. Sporn J. Kehrl
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1986
Further data are obtained to support a role for TGF-beta as an intrinsic mediator of collagen formation: conditioned media obtained from activated human tonsillar T lymphocytes contain greatly elevated levels of T GF-beta compared tomedia obtained from unactivated lymphocytes.

Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis.

It is demonstrated that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.

A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene.

Northern blot and run-on transcription assays indicate that TGF-beta directly activates transcription of the CTGF gene, and analysis of deletion mutants indicated that an important T GF-beta regulatory element is located between positions -162 and -128 of theCTGF promoter sequence.

Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.

The results demonstrate a functional involvement of fibronectin in mediating cellular responses to TGFbeta, and suggest a model for TGF beta action based on the control of the extracellular matrix in target cells.