scholarly journals Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo

2009 ◽  
Vol 3 (1) ◽  
pp. 5-18 ◽  
Author(s):  
David R. Brigstock
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Pharmacological Inhibition ◽  
Sirna Therapy

scholarly journals Acceleration of Osteogenesis via Stimulation of Angiogenesis by Combination with Scaffold and Connective Tissue Growth Factor

Materials ◽  
2019 ◽  
Vol 12 (13) ◽  
pp. 2068 ◽  
Author(s):  
Michiyo Honda ◽  
Ryo Hariya ◽  
Morio Matsumoto ◽  
Mamoru Aizawa
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Cell Interaction ◽  
Tissue Growth ◽  
Matrix Remodeling ◽  
Bioactive Materials ◽  
Stimulation Of

In bone regeneration, there are some important cellular biological processes, such as mineralization, cell organization, and differentiation. In particular, vascularization into regenerative tissues is a key step for the survival of cells and tissues. In this study, to fabricate biomimetic-engineered bone, including vascular networks, we focused on connective tissue growth factor (CTGF), a multifunctional protein which could regulate the extracellular matrix remodeling. By combination with CTGF and hydroxyapatite (HAp) ceramics (2D) or apatite-fiber scaffold (AFS, 3D), we have fabricated bioactive materials. The CTGF-loaded HAp ceramics could enhance the cellular attachment through interaction with integrin and promote actin cytoskeletal reorganization. CTGF-loaded HAp also enhanced the differentiation of osteoblasts by integrin-mediated activation of the signaling pathway. Under co-culture conditions, both osteoblasts and endothelial cells in the CTGF-loaded AFS were stimulated by CTGF, and each cell could penetrate the central region of the scaffold in vitro and in vivo. Direct cell-cell interaction would also improve the functionality of cells in bone formation. These results suggest that coupling between effective optimized scaffold and CTGF with multifunction could provide better mimicking natural bone by stimulation of angiogenesis.

scholarly journals Connective tissue growth factor causes EMT-like cell fate changes in vivo and in vitro

2013 ◽  
Vol 126 (10) ◽  
pp. 2164-2175 ◽  
Author(s):  
S. Sonnylal ◽  
S. Xu ◽  
H. Jones ◽  
A. Tam ◽  
V. R. Sreeram ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Cell Fate ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth

Connective tissue growth factor/CCN-2 is upregulated in epididymal and subcutaneous fat depots in a dietary-induced obesity model

2013 ◽  
Vol 304 (12) ◽  
pp. E1291-E1302 ◽  
Author(s):  
Joanne T. M. Tan ◽  
Susan V. McLennan ◽  
Paul F. Williams ◽  
Alireza Rezaeizadeh ◽  
Lisa W.-Y. Lo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Adipocyte Differentiation ◽  
Subcutaneous Fat ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Fat Depots

Connective tissue growth factor (CTGF), also known as CCN-2, is a cysteine-rich secreted protein that is involved in a range of biological processes, including regulation of cell growth and differentiation. Our previous in vitro studies have shown that CCN-2 inhibits adipocyte differentiation, although whether CCN-2 is regulated in vivo in adipogenesis is undetermined and was investigated in this study. C57BL/6 male mice were fed either standard laboratory chow (ND) or a diet high in fat (HFD; 45% fat) for 15 or 24 wk. HFD animals that gained >5 g in weight (termed HFD-fat) were insulin resistant and were compared with HFD-fed animals, which failed to gain weight (termed HFD-lean). HFD-fat mice had significantly increased CCN-2 mRNA levels in both the subcutaneous and epididymal fat pads, whereas CCN-2 mRNA was not induced in the epididymal site in HFD-lean mice. Also in HFD-fed animals, epididymal CCN-2 mRNA correlated positively with key genes involved in adipocyte differentiation, adiponectin and PPARγ ( P < 0.001 and P < 0.002, respectively). Additionally, epididymal CCN-2 mRNA correlated positively with two markers of tissue turnover, PAI-1 in HFD-fat mice only and TIMP-1, but only in the HFD-lean mice. Collectively, these findings suggest that CCN-2 plays a role in adipocyte differentiation in vivo and thus in the pathogenesis of obesity linked with insulin resistance.

scholarly journals Connective-Tissue Growth Factor (CTGF/CCN2) Induces Astrogenesis and Fibronectin Expression of Embryonic Neural Cells In Vitro

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0133689 ◽  
Author(s):  
Fabio A. Mendes ◽  
Juliana M. Coelho Aguiar ◽  
Suzana A. Kahn ◽  
Alice H. Reis ◽  
Luiz Gustavo Dubois ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Neural Cells ◽  
Fibronectin Expression

scholarly journals CCN2 (Connective Tissue Growth Factor) Promotes Fibroblast Adhesion to Fibronectin

2004 ◽  
Vol 15 (12) ◽  
pp. 5635-5646 ◽  
Author(s):  
Yunliang Chen ◽  
David J. Abraham ◽  
Xu Shi-wen ◽  
Jeremy D. Pearson ◽  
Carol M. Black ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Growth Factor ◽  
Protein Kinase ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Fibroblast Adhesion

In vivo, CCN2 (connective tissue growth factor) promotes angiogenesis, osteogenesis, tissue repair, and fibrosis, through largely unknown mechanisms. In vitro, CCN2 promotes cell adhesion in a variety of systems via integrins and heparin sulfate proteoglycans (HSPGs). However, the physiological relevance of CCN2-mediated cell adhesion is unknown. Here, we find that HSPGs and the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade are required for adult human dermal fibroblasts to adhere to CCN2. Endogenous CCN2 directly binds fibronectin and the fibronectin receptors integrins α4 β1 and α5 and syndecan 4. Using Ccn2-/- mouse embryonic fibroblasts, we show that loss of endogenous CCN2 results in impaired spreading on fibronectin, delayed α-smooth muscle actin stress fiber formation, and reduced ERK and focal adhesion kinase phosphorylation. These results suggest that a physiological role of CCN2 is to potentiate the ability of fibroblasts to spread on fibronectin, which may be important in modulating fibroblast adhesion to the provisional matrix during tissue development and wound healing. These results are consistent with the notion that a principal function of CCN2 is to modulate receptor/ligand interactions in vivo.

scholarly journals Keratinocytes Inhibit Expression of Connective Tissue Growth Factor in Fibroblasts In Vitro by an Interleukin-1α-Dependent Mechanism

2002 ◽  
Vol 119 (2) ◽  
pp. 449-455 ◽  
Author(s):  
Daniel Nowinski ◽  
Patrik Höijer ◽  
Thomas Engstrand ◽  
Bengt Gerdin ◽  
Mikael Ivarsson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Interleukin 1Α ◽  
Dependent Mechanism

scholarly journals Decorin Interacts with Connective Tissue Growth Factor (CTGF)/CCN2 by LRR12 Inhibiting Its Biological Activity

2011 ◽  
Vol 286 (27) ◽  
pp. 24242-24252 ◽  
Author(s):  
Cecilia Vial ◽  
Jaime Gutiérrez ◽  
Cristian Santander ◽  
Daniel Cabrera ◽  
Enrique Brandan
Keyword(s):  
Biological Activity ◽  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Core Protein ◽  
Tissue Growth ◽  
Collagen Iii ◽  
Fibrotic Disorders ◽  
Leucine Rich Repeats

Fibrotic disorders are the end point of many chronic diseases in different tissues, where an accumulation of the extracellular matrix occurs, mainly because of the action of the connective tissue growth factor (CTGF/CCN2). Little is known about how this growth factor activity is regulated. We found that decorin null myoblasts are more sensitive to CTGF than wild type myoblasts, as evaluated by the accumulation of fibronectin or collagen III. Decorin added exogenously negatively regulated CTGF pro-fibrotic activity and the induction of actin stress fibers. Using co-immunoprecipitation and in vitro interaction assays, decorin and CTGF were shown to interact in a saturable manner with a Kd of 4.4 nm. This interaction requires the core protein of decorin. Experiments using the deletion mutant decorin indicated that the leucine-rich repeats (LRR) 10–12 are important for the interaction with CTGF and the negative regulation of the cytokine activity, moreover, a peptide derived from the LRR12 was able to inhibit CTGF-decorin complex formation and CTGF activity. Finally, we showed that CTGF specifically induced the synthesis of decorin, suggesting a mechanism of autoregulation. These results suggest that decorin interacts with CTGF and regulates its biological activity.

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