Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Apr 25;25(9):4692.
doi: 10.3390/ijms25094692.

Connective Tissue Growth Factor: Regulation, Diseases, and Drug Discovery

Meishen Ren  1   2 , Shanshan Yao  3 , Tienan Chen  2 , Hang Luo  3 , Xiaohui Tao  2 , Hewen Jiang  3 , Xin Yang  2 , Huarui Zhang  3 , Sifan Yu  3 , Yin Wang  1 , Aiping Lu  2 , Ge Zhang  2
Affiliations
Review

Connective Tissue Growth Factor: Regulation, Diseases, and Drug Discovery

Meishen Ren et al. Int J Mol Sci. .

Abstract

In drug discovery, selecting targeted molecules is crucial as the target could directly affect drug efficacy and the treatment outcomes. As a member of the CCN family, CTGF (also known as CCN2) is an essential regulator in the progression of various diseases, including fibrosis, cancer, neurological disorders, and eye diseases. Understanding the regulatory mechanisms of CTGF in different diseases may contribute to the discovery of novel drug candidates. Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery.

Keywords: CTGF-related diseases; CTGF/CCN2; drug discovery; regulation mechanism; therapeutic target.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Three-dimensional structure of the CTGF protein. The human CTGF structural PDB file was obtained from the AlphaFold Protein Structure Database (https://alphafold.com/, accessed on 7 April 2024).
Figure 2
Figure 2
Diagram of the interaction network between CTGF’s domains and different molecules, signaling pathways, and diseases. Abbreviations: BMP, bone morphogenetic proteins; CT, cysteine knot-containing domain; EGF, epidermal growth factor; ER, estrogen receptors; FAK, focal adhesion kinase; FGFs, fibroblast growth factors; HSPG, heparan sulfate proteoglycan; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; LATS, long-acting thyroid stimulator; LRP, low-density lipoprotein receptor-related protein; MRTF-A, myocardin-related transcription factor A; RhoA, ras homolog family member A; SLIT2, slit guidance ligand 2; TGF-β, transforming growth factor-β; TSP-1, thrombospondin type-1 repeat; VWC, von Willebrand factor type C repeat; Wif, Wnt inhibitory factor; YAP, Yes-associated protein.
Figure 3
Figure 3
Structures of marketed compounds for CTGF-targeted and -inhibitory therapy. The chemical structures were obtained from the Drugbank online database (https://go.drugbank.com/, accessed on 7 April 2024).
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Fu M., Peng D., Lan T., Wei Y., Wei X. Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases. Acta Pharm. Sin. B. 2022;12:1740–1760. doi: 10.1016/j.apsb.2022.01.007. - DOI - PMC - PubMed
    1. Shen Y.-W., Zhou Y.-D., Chen H.-Z., Luan X., Zhang W.-D. Targeting CTGF in cancer: An emerging therapeutic opportunity. Trends Cancer. 2021;7:511–524. doi: 10.1016/j.trecan.2020.12.001. - DOI - PubMed
    1. Wu Z., Zhou C., Yuan Q., Zhang D., Xie J., Zou S. CTGF facilitates cell-cell communication in chondrocytes via PI3K/Akt signalling pathway. Cell Prolif. 2021;54:e13001. doi: 10.1111/cpr.13001. - DOI - PMC - PubMed
    1. Hendesi H., Barbe M.F., Safadi F.F., Monroy M.A., Popoff S.N. Integrin mediated adhesion of osteoblasts to connective tissue growth factor (CTGF/CCN2) induces cytoskeleton reorganization and cell differentiation. PLOS ONE. 2015;10:e0115325. doi: 10.1371/journal.pone.0115325. - DOI - PMC - PubMed
    1. Cheng J.-C., Wang E.Y., Yi Y., Thakur A., Tsai S.-H., Hoodless P.A. S1P stimulates proliferation by upregulating CTGF expression through S1PR2-mediated YAP activation. Mol. Cancer Res. 2018;16:1543–1555. doi: 10.1158/1541-7786.mcr-17-0681. - DOI - PubMed

Substances