Expression and clinical significance of connective tissue growth factor (CTGF) in Graves' ophthalmopathy

Huang, Yi; Chang, Pei Chen; Wu, Shengjun; Kau, Hui-Chuan; Tsai, Chieh Chih; Liu, Catherine Jui Ling; Wei, Yau‐Huei

doi:10.1136/bjophthalmol-2016-308713

Cited by 8 publications

(8 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we found that the plasma CTGF levels positively correlated with the levels of FT3 and TRAb. Similarly, Huang et al reported that the levels of CTGF expression in orbital broblasts in Graves' ophthalmopathy showed a signi cant positively correlation with serum levels of TRAb; however, a correlation between the levels of CTGF expression and FT3 were not be found [31]. Although the above mentioned results do not absolutely match those in this study, the circulating levels of CTGF may be more representative of systemic conditions than that in orbital broblasts.…”

Section: Discussioncontrasting

confidence: 73%

The association of plasma connective tissue growth factor (CTGF) levels with hyperthyroidism heart disease: a cross-sectional observational study

Zeng

Liao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Hyperthyroidism heart disease (HHD) is the most severe complication of overt hyperthyroidism and increases the mortality risk in affected patients. Early identification of patients at a higher risk of developing HHD could improve clinical outcomes through active surveillance and management. Connective tissue growth factor (CTGF), a secreted extracellular protein, plays a significant role in cardiac remodeling and dysfunction. We aimed to investigate the relationship between plasma CTGF level and the risk of HHD in this study.Methods: A total of 142 overt hyperthyroidism patients without HHD and 99 patients with HHD were included. The plasma CTGF levels were measured via ELISA. Routine clinical medical data and echocardiography parameters were also recorded.Results: The plasma CTGF level was significantly higher in patients with HHD than in those without HHD (P = 0.002) and positively correlated with the levels of FT3, TRAb, TnI, LDH and the left atrium diameter, right atrium diameter, and right ventricular end-diastolic diameter(all P < 0.05). Logistic regression analysis showed that quartile 3 and 4 of plasma CTGF levels were significantly associated with the increased risk of HHD (crude OR 2.529; 95% CI 1.188-5.387). However, after adjustment for the potentially confounding variables, only quartile 4 was significantly associated with the higher risk of HHD relative to quartile 1.Conclusions: Hyperthyroidism patients with HHD display higher plasma CTGF levels. Furthermore, CTGF is an independent risk factor for HHD. Therefore, the plasma CTGF level may be a potential biomarker for the risk of HHD.

show abstract

Section: Discussioncontrasting

confidence: 73%

The association of plasma connective tissue growth factor (CTGF) levels with hyperthyroidism heart disease: a cross-sectional observational study

Zeng

Liao

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…On the other hand, CTGF was found to modulate myofibroblast activation, extracellular matrix deposition, angiogenesis, and tissue remodeling [34]. Previous studies have demonstrated a higher baseline CTGF expression level in GO orbital fibroblasts compared to the normal control [35], and the expression level of CTGF of GO orbital fibroblasts was found to be significantly associated with the clinical progression of GO [36]. In addition, the essential role of CTGF in TGF-β1-induced myofibroblast differentiation of GO orbital fibroblasts has been confirmed by knockdown of CTGF via small hairpin RNA of the CTGF gene [22].…”

Section: Discussionmentioning

confidence: 98%

Curcumin Suppresses TGF-β1-Induced Myofibroblast Differentiation and Attenuates Angiogenic Activity of Orbital Fibroblasts

Hwang

Wang

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Orbital fibrosis, a hallmark of tissue remodeling in Graves’ ophthalmopathy (GO), is a chronic, progressive orbitopathy with few effective treatments. Orbital fibroblasts are effector cells, and transforming growth factor β1 (TGF-β1) acts as a critical inducer to promote myofibroblast differentiation and subsequent tissue fibrosis. Curcumin is a natural compound with anti-fibrotic activity. This study aims to investigate the effects of curcumin on TGF-β1-induced myofibroblast differentiation and on the pro-angiogenic activities of orbital fibroblasts. Orbital fibroblasts from one healthy donor and three patients with GO were collected for primary cell culture and subjected to myofibroblast differentiation under the administration of 1 or 5 ng/mL TGF-β1 for 24 h. The effects of curcumin on TGF-β1-induced orbital fibroblasts were assessed by measuring the cellular viability and detecting the expression of myofibroblast differentiation markers, including connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA). The pro-angiogenic potential of curcumin-treated orbital fibroblasts was evaluated by examining the transwell migration and tube-forming capacities of fibroblast-conditioned EA.hy926 and HMEC-1 endothelial cells. Treatment of orbital fibroblasts with curcumin inhibited the TGF-β1 signaling pathway and attenuated the expression of CTGF and α-SMA induced by TGF-β1. Curcumin, at the concentration of 5 μg/mL, suppressed 5 ng/mL TGF-β1-induced pro-angiogenic activities of orbital fibroblast-conditioned EA hy926 and HMEC-1 endothelial cells. Our findings suggest that curcumin reduces the TGF-β1-induced myofibroblast differentiation and pro-angiogenic activity in orbital fibroblasts. The results support the potential application of curcumin for the treatment of GO.

show abstract

“…We recently demonstrated that mRNA and protein expression levels of CTGF were significantly increased in GO orbital fibroblasts compared with normal fibroblasts 15 . In addition, the elevated CTGF in GO orbital fibroblasts was associated with the clinical evolution of GO 16 . Noteworthily, it is required to unravel how the upregulation of CTGF contributed to the pathophysiology of GO.…”

Section: Introductionmentioning

confidence: 94%

Essential role of connective tissue growth factor (CTGF) in transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from Graves’ orbital fibroblasts

Tsai

Kau

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

Connective tissue growth factor (CTGF) associated with transforming growth factor-β (TGF-β) play a pivotal role in the pathophysiology of many fibrotic disorders. However, it is not clear whether this interaction also takes place in GO. In this study, we investigated the role of CTGF in TGF-β-induced extracellular matrix production and myofibroblast transdifferentiation in Graves’ orbital fibroblasts. By Western blot analysis, we demonstrated that TGF-β1 induced the expression of CTGF, fibronectin, and alpha-smooth muscle actin (α-SMA) in Graves’ orbital fibroblasts. In addition, the protein levels of fibronectin and α-SMA in Graves’ orbital fibroblasts were also increased after treatment with a recombinant human protein CTGF (rhCTGF). Moreover, we transfected the orbital fibroblasts with a small hairpin RNA of CTGF gene (shCTGF) to knockdown the expression levels of CTGF, which showed that knockdown of CTGF significantly diminished TGF-β1-induced expression of CTGF, fibronectin and α-SMA proteins in Graves’ orbital fibroblasts. Furthermore, the addition of rhCTGF to the shCTGF-transfected orbital fibroblasts could restore TGF-β1-induced expression of fibronectin and α-SMA proteins. Our findings demonstrate that CTGF is an essential downstream mediator for TGF-β1-induced extracellular matrix production and myofibroblast transdifferentiation in Graves’ orbital fibroblasts and thus may provide with a potential therapeutic target for treatment of GO.

show abstract

Expression and clinical significance of connective tissue growth factor (CTGF) in Graves' ophthalmopathy

Cited by 8 publications

References 47 publications

The association of plasma connective tissue growth factor (CTGF) levels with hyperthyroidism heart disease: a cross-sectional observational study

The association of plasma connective tissue growth factor (CTGF) levels with hyperthyroidism heart disease: a cross-sectional observational study

Curcumin Suppresses TGF-β1-Induced Myofibroblast Differentiation and Attenuates Angiogenic Activity of Orbital Fibroblasts

Essential role of connective tissue growth factor (CTGF) in transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from Graves’ orbital fibroblasts

Contact Info

Product

Resources

About