The opposing effects of CCN2 and CCN5 on the development of cardiac hypertrophy and fibrosis

Yoon, Pyoung Oh; Lee, Min-Ah; Cha, Hyeseon; Jeong, Moon Hee; Kim, Jooyeon; Jang, Seung Pil; Choi, Bo Youn; Jeong, Dongtak; Yang, Dong Kwon; Hajjar, Roger J.; Park, Woo Jin

doi:10.1016/j.yjmcc.2010.04.010

Cited by 120 publications

(141 citation statements)

References 39 publications

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“…Consistent with such findings, the present study suggests that CCN3 plays a distinct role as "yin"; whereas that of "yang" may be played by the collaboration of several other CCN family members. However, it should noted that a recent report indicated that CCN5, which is the only CCN family member lacking the CT module, functions to counteract CCN2 (Yoon et al 2010). Thus, comprehensive analysis of all of the CCN members is of critical importance for better understanding of the functional properties of the CCN family members.…”

Section: Discussionmentioning

confidence: 99%

Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family

Kader

Kubota

Janune

et al. 2012

J. Cell Commun. Signal.

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CCN family proteins 2 and 3 (CCN2 and CCN3) belong to the CCN family of proteins, all having a high level of structural similarity. It is widely known that CCN2 is a profibrotic molecule that mediates the development of fibrotic disorders in many different tissues and organs. In contrast, CCN3 has been recently suggested to act as an anti-fibrotic factor in several tissues. This CCN3 action was shown earlier to be exerted by the repression of the CCN2 gene expression in kidney tissue, whereas different findings were obtained for liver cells. Thus, the molecular action of CCN3 yielding its anti-fibrotic effect is still controversial. Here, using a general model of fibrosis, we evaluated the effect of CCN3 overexpression on the gene expression of all of the CCN family members, as well as on that of fibrotic marker genes. As a result, repression of CCN2 gene expression was modest, while type I collagen and α-smooth muscle actin gene expression was prominently repressed. Interestingly, not only CCN2, but also CCN4 gene expression showed a decrease upon CCN3 overexpression. These findings indicate that fibrotic gene induction is under the control of a complex molecular network conducted by CCN family members functioning together.

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Section: Discussionmentioning

confidence: 99%

Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family

Kader

Kubota

Janune

et al. 2012

J. Cell Commun. Signal.

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“…The second vector, lnv-CTGF-⌬CT, is a mutant form of the CTGF/CCN2 protein lacking the C-terminal domain. This mutant variant acts as a dominant negative form of the wild type protein and inhibits CTGF/CCN2 activity (32,33). The expression and migratory pattern of CTGF-⌬CT as compared with the full-length CTGF/CCN2 protein were confirmed by gel electrophoresis of retinal protein homogenates from eyes injected with either lnv-luc, lnv-CTGF, or lnv-CTGF-⌬CT (supplemental Fig.…”

Section: Effects Of Ctgf/ccn2 Depletion On Hyperoxia-induced Retinal mentioning

confidence: 92%

“…Fragments of CTGF/CCN2 have been shown to accumulate in tissue culture or body fluids, and these fragments may retain biological activity distinct from the intact protein (32). Deletion of the CT domain of CTGF/ CCN2 generates a dominant negative variant that antagonizes the activity of the native CTGF/CCN2 molecule (33). Thus, the multimodular organization of the CTGF/CCN2 protein is a means of generating through proteolytic cleavage, variants/bioactive domains that exhibit a diverse range of activities and perhaps bioavailabilities in different milieux.…”

mentioning

confidence: 99%

Connective Tissue Growth Factor Regulates Retinal Neovascularization through p53 Protein-dependent Transactivation of the Matrix Metalloproteinase (MMP)-2 Gene

Chintala

Parmar

et al. 2012

Journal of Biological Chemistry

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“…Moreover, as some members of the CCN family, notably CCN3 and CCN5 block the fibrogenic action of CCN2, it is possible that CCN3 and CCN5 may be used in the future to treat fibrotic diseases such as SSc (Riser et al 2009;Leask 2009;Yoon et al 2010). …”

Section: Connective Tissue Growth Factor (Ctgf Ccn2)mentioning

confidence: 99%

Possible strategies for anti-fibrotic drug intervention in scleroderma

Leask

2011

J. Cell Commun. Signal.

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There are no approved drugs for treating the fibrosis in scleroderma (systemic sclerosis, SSc). Myfibroblasts within connective tissue express the highly contractile protein α-smooth muscle actin (α-SMA) and are responsible for the excessive synthesis and remodeling of extracellular matrix (ECM) characterizing SSc. Drugs targeting myofibroblast differentiation, recruitment and activity are currently under consideration as anti-fibrotic treatments in SSc but thus far have principally focused on the transforming growth factor β (TGFβ), endothelin-1 (ET-1), connective tissue growth factor (CCN2/CTGF) and platelet derived growth factor (PDGF) pathways, which display substantial signaling crosstalk. Moreover, peroxisome proliferator-activated receptor (PPAR)γ also appears to act by intervening in TGFβ signaling. This review discusses these potential candidates for antifibrotic therapy in SSc.

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The opposing effects of CCN2 and CCN5 on the development of cardiac hypertrophy and fibrosis

Cited by 120 publications

References 39 publications

Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family

Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family

Connective Tissue Growth Factor Regulates Retinal Neovascularization through p53 Protein-dependent Transactivation of the Matrix Metalloproteinase (MMP)-2 Gene

Possible strategies for anti-fibrotic drug intervention in scleroderma

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