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Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases.

ABSTRACT: Connective tissue growth factor (CTGF), a multifunctional protein of the CCN family, regulates cell proliferation, differentiation, adhesion, and a variety of other biological processes. It is involved in the disease-related pathways such as the Hippo pathway, p53 and nuclear factor kappa-B (NF-κB) pathways and thus contributes to the developments of inflammation, fibrosis, cancer and other diseases as a downstream effector. Therefore, CTGF might be a potential therapeutic target for treating various diseases. In recent years, the research on the potential of CTGF in the treatment of diseases has also been paid more attention. Several drugs targeting CTGF (monoclonal antibodies FG3149 and FG3019) are being assessed by clinical or preclinical trials and have shown promising outcomes. In this review, the cellular events regulated by CTGF, and the relationships between CTGF and pathogenesis of diseases are systematically summarized. In addition, we highlight the current researches, focusing on the preclinical and clinical trials concerned with CTGF as the therapeutic target.

SUBMITTER: Fu M

PROVIDER: S-EPMC9279711 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases.

Fu Minyang M Peng Dandan D Lan Tianxia T Wei Yuquan Y Wei Xiawei X

Acta pharmaceutica Sinica. B 20220119 4

Connective tissue growth factor (CTGF), a multifunctional protein of the CCN family, regulates cell proliferation, differentiation, adhesion, and a variety of other biological processes. It is involved in the disease-related pathways such as the Hippo pathway, p53 and nuclear factor kappa-B (NF-<i>κ</i>B) pathways and thus contributes to the developments of inflammation, fibrosis, cancer and other diseases as a downstream effector. Therefore, CTGF might be a potential therapeutic target for trea ...[more]

PMID: 35847511

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Project description:Connective-tissue growth factor (CTGF/CCN2) is a matricellular-secreted protein involved in complex processes such as wound healing, angiogenesis, fibrosis and metastasis, in the regulation of cell proliferation, migration and extracellular matrix remodeling. Glioblastoma (GBM) is the major malignant primary brain tumor and its adaptation to the central nervous system microenvironment requires the production and remodeling of the extracellular matrix. Previously, we published an in vitro approach to test if neurons can influence the expression of the GBM extracellular matrix. We demonstrated that neurons remodeled glioma cell laminin. The present study shows that neurons are also able to modulate CTGF expression in GBM. CTGF immnoreactivity and mRNA levels in GBM cells are dramatically decreased when these cells are co-cultured with neonatal neurons. As proof of particular neuron effects, neonatal neurons co-cultured onto GBM cells also inhibit the reporter luciferase activity under control of the CTGF promoter, suggesting inhibition at the transcription level. This inhibition seems to be contact-mediated, since conditioned media from embryonic or neonatal neurons do not affect CTGF expression in GBM cells. Furthermore, the inhibition of CTGF expression in GBM/neuronal co-cultures seems to affect the two main signaling pathways related to CTGF. We observed inhibition of TGFβ luciferase reporter assay; however phopho-SMAD2 levels did not change in these co-cultures. In addition levels of phospho-p44/42 MAPK were decreased in co-cultured GBM cells. Finally, in transwell migration assay, CTGF siRNA transfected GBM cells or GBM cells co-cultured with neurons showed a decrease in the migration rate compared to controls. Previous data regarding laminin and these results demonstrating that CTGF is down-regulated in GBM cells co-cultured with neonatal neurons points out an interesting view in the understanding of the tumor and cerebral microenvironment interactions and could open up new strategies as well as suggest a new target in GBM control.

Project description:Primordial follicle assembly is a process that occurs in the embryonic or early post natal ovary in which oocyte nests break down to form individual primordial follicles. The size of this initial pool of primordial follicles in part determines the reproductive lifespan of the female. Connective tissue growth factor (CTGF) was identified as a potential regulatory candidate for this process in a previous microarray analysis of follicle development. The current study examines the effects of CTGF and associated transforming growth factor beta 1 (TGFbeta-1) on follicle assembly. Ovaries were removed from newborn rat pups and placed in an organ culture system for two days to measure the effect of these factors on follicle assembly. In addition, ovaries were cultured and treated for ten days to determine the potential of CTGF and TGFbeta-1 to manipulate the primordial follicle pool size over a longer developmental time period. The ovaries treated with CTGF for two days were found to have an increased proportion of assembled follicles. TGFbeta-1 had no effect on primordial follicle assembly and in combination with CTGF decreased oocyte number in the ovary after two days of culture. Over ten days of treatment only the combined treatment of CTGF and TGFbeta-1 was found to cause an increase in the proportion of assembled follicles. Interestingly, treatment with TGFbeta-1 alone resulted in fewer total oocytes in the ovary and decreased the primordial follicle pool size after ten days of culture. Observations indicate that CTGF alone or in combination with TGFbeta-1 stimulates primordial follicle assembly and TGFbeta-1 can decrease the primordial follicle pool size. CTGF was found to regulate the ovarian transcriptome during primordial follicle assembly and an integrative network of genes was identified. CTGF is one of the first growth factors shown to promote primordial follicle assembly, while TGFbeta-1 is one of the first factors shown to decrease the primordial follicle pool size. These observations suggest the possibility of manipulating primordial follicle pool size and influencing female reproductive lifespan. We used microarrays to determine genes expressed differentially between control and CTGF (connective tissue growth factor) treated P0 ovary

Dataset Information

Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases.

Publications

Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases.

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