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

Fu, Minyang; Peng, Dandan; Lan, Tu; Wei, Yuquan; Wei, Xiawei

doi:10.1016/j.apsb.2022.01.007

Cited by 39 publications

(21 citation statements)

References 321 publications

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“…CTGF is involved in pathophysiological processes such as wound repair, angiogenesis, and cell proliferation, migration, and differentiation. 8, 9 A previous study found that plasma CTGF concentrations have good diagnostic and predictive value for CHD-PAH in children. 10 In another study of 30 children with CHD-PAH, CTGF was recognized as a promising biomarker for CHD-PAH in children, but there was no significant correlation between CTGF and hemodynamic parameters, so it could not be used to evaluate the severity of PAH.…”

Section: Discussionmentioning

confidence: 98%

Plasma Connective Tissue Growth Factor as a Biomarker of Pulmonary Arterial Hypertension Associated With Congenital Heart Disease in Adults

Liu

Huang

Zheng

et al. 2023

Circ J

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Background: Connective tissue growth factor (CTGF) has diagnostic value for pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) in children; however, its value in adult patients remains unclear. This study evaluated CTGF as a biomarker in adult PAH-CHD patients. Methods and Results:Based on mean pulmonary artery pressure (mPAP), 56 CHD patients were divided into 3 groups: without PAH (W; mPAP <25 mmHg; n=28); mild PAH (M; mPAP 25-35 mmHg; n=18); and moderate and severe PAH (H; mPAP ≥35 mmHg; n=10). The control group consisted of 28 healthy adults. Plasma CTGF and B-type natriuretic peptide (BNP) concentrations were determined. Plasma CTGF concentrations were higher in the H and M groups than in the W and control groups, and were higher in the H than M group. Plasma CTGF concentrations were positively correlated with pulmonary artery systolic pressure (PASP), mPAP, and pulmonary vascular resistance, and negatively correlated with mixed venous oxygen saturation. CTGF, BNP, red blood cell distribution width, and World Health Organization Class III/IV were risk factors for PAH in CHD patients, and CTGF was an independent risk factor for PAH-CHD. The efficacy of CTGF in the diagnosis of PAH was not inferior to that of BNP. Conclusions:CTGF is a biomarker of PAH associated with CHD. It can be used for early diagnosis and severity assessment in adult patients with CHD-PAH.

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Section: Discussionmentioning

confidence: 98%

Plasma Connective Tissue Growth Factor as a Biomarker of Pulmonary Arterial Hypertension Associated With Congenital Heart Disease in Adults

Liu

Huang

Zheng

et al. 2023

Circ J

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“…It is a multifunctional protein in the CCN family that regulates the cell proliferation, differentiation, adhesion and various other biological processes. It is involved in disease-related pathways such as the Hippo pathway, p53 and nuclear factor Kappa-B (NF-κB) pathway, and thus contributes as a downstream effector to the development of inflammation, fibrosis, cancer and other diseases [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Transcriptomic and Proteomic of Corynebacterium pseudotuberculosis Infection in the Spleen of Dairy Goats

Cheng

et al. 2022

Animals

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Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a zoonotic chronic infectious disease. It mainly occurs in dairy goats reared in herds, and once it invades the dairy goats, it is difficult to completely remove it, causing great harm to the development of the sheep industry. This study mainly was based on TMT-based quantitative proteomics and RNA-seq methods to measure the spleen samples of infected dairy goats at different time periods. Nine four-month-old dairy goats were divided into three groups, with three goats in each group. The dairy goats in the first group (NC group) were inoculated with 1.0 mL of sterilized normal saline subcutaneously, and the second (72 h group) and third groups (144 h group) were inoculated with 1.0 mL of 1 × 107 cfu/mL bacterial solution subcutaneously in the neck. Significant changes in the protein and mRNA expression were observed in different infection and control groups. In the 72 h group, 85 genes with differential genes and proteins were up-regulated and 91 genes were down-regulated in this study. In the 144 h group, 38 genes with differential genes and proteins were up-regulated and 51 genes were down-regulated. It was found that 21 differentially expressed genes and proteins were co-up-regulated in the two groups. There were 20 differentially expressed genes and proteins which were co-down-regulated in both groups. The 72 h group were mainly enriched in protein processing in the endoplasmic reticulum, lysosome, amino sugar and nucleotide sugar metabolism and the estrogen signaling pathway. In the 144 h group, they were protein processing in the endoplasmic reticulum pathway which was enriched by mRNA–proteins pairs co-upregulated by the five pairs. The combined transcriptomic and proteomic analyses were performed to provide insights into the effects of C. pseudotuberculosis through several regulatory features and pathways. We found that in the early stage of infection (72 h), the co-upregulated gene–protein pairs were enriched in multiple pathways, which jointly defended against a bacterial invasion. However, in the later stages of infection (144 h), when the disease stabilizes, a few co-upregulated gene–protein pairs played a role in protein processing in the endoplasmic reticulum pathway. In addition, the mRNA and protein expressions of dairy goats infected with the bacteria at different periods of time indicated the adaptability of dairy goats to the bacteria. At the same time, it guides us to carry out a corresponding treatment and feeding management for dairy goats according to different periods of time.

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“…Cell viability was examined by using Alamar Blue migration, proliferation, survival, and cross-talk of tumor cell and ECM), and miRNA-199a and -214. Those targets can be inhibited by delivering their inhibitors or antibodies resulting in reduction of CAF-induced matrix barrier and thus improve nanomedicine penetration [51][52][53][54][55][56][57][58][59]. Antifibrotic drugs such as pirfenidone can also suppressed CAF-promoted tumor progression [60,61].…”

Section: In Vitro Effect Of Ptx-loaded Pmc and Pnps In 2d Cell Cultur...mentioning

confidence: 99%

Evaluation of paclitaxel-loaded polymeric nanoparticles in 3D tumor model: impact of tumor stroma on penetration and efficacy

Priwitaningrum

Pednekar

Gabriël

et al. 2023

Drug Deliv. and Transl. Res.

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Since tumor stroma poses as a barrier to achieve efficacy of nanomedicines, it is essential to evaluate nano-chemotherapeutics in stroma-mimicking 3D models that reliably predict their behavior regarding these hurdles limiting efficacy. In this study, we evaluated the effect of paclitaxel-loaded polymeric micelles (PTX-PMCs) and polymeric nanoparticles (PTX-PNPs) in a tumor stroma–mimicking 3D in vitro model. PTX-PMCs (77 nm) based on a amphiphilic block copolymer of mPEG-b-p(HPMAm-Bz) and PTX-PNPs (159 nm) based on poly(lactic-co-glycolic acid) were prepared, which had an encapsulation efficiency (EE%) of 81 ± 15% and 45 ± 8%, respectively. 3D homospheroids of mouse 4T1 breast cancer cells and heterospheroids of NIH3T3 fibroblasts and 4T1 (5:1 ratio) were prepared and characterized with high content two-photon microscopy and immunostaining. Data showed an induction of epithelial-mesenchymal transition (α-SMA) in both homo- and heterospheroids, while ECM (collagen) deposition only in heterospheroids. Two-photon imaging revealed that both fluorescently labeled PMCs and PNPs penetrated into the core of homospheroids and only PMCs penetrated into heterospheroids. Furthermore, PTX-PMCs, PTX-PNPs, and free PTX induced cytotoxicity in tumor cells and fibroblasts grown as monolayer, but these effects were substantially reduced in 3D models, in particular in heterospheroids. Gene expression analysis showed that heterospheroids had a significant increase of drug resistance markers (Bcl2, Abgc2) compared to 2D or 3D monocultures. Altogether, this study shows that the efficacy of nanotherapeutics is challenged by stroma-induced poor penetration and development of resistant phenotype. Therefore, this tumor stroma–mimicking 3D model can provide an excellent platform to study penetration and effects of nanotherapeutics before in vivo studies. Graphical Abstract

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

Cited by 39 publications

References 321 publications

Plasma Connective Tissue Growth Factor as a Biomarker of Pulmonary Arterial Hypertension Associated With Congenital Heart Disease in Adults

Plasma Connective Tissue Growth Factor as a Biomarker of Pulmonary Arterial Hypertension Associated With Congenital Heart Disease in Adults

Combined Transcriptomic and Proteomic of Corynebacterium pseudotuberculosis Infection in the Spleen of Dairy Goats

Evaluation of paclitaxel-loaded polymeric nanoparticles in 3D tumor model: impact of tumor stroma on penetration and efficacy

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