The Role of CTGF in Inflammatory Responses Induced by Silica Particles in Human Bronchial Epithelial Cells

Zhou, Ting; Yu, Qimei; Lin, Hui; Wang, Zhenyu; Fu, Guoqing; Lü, Lei; Shi, Yuqin; Zhang, Ling; Qin, Lingzhi; Liu, Yuewei

doi:10.1007/s00408-019-00272-x

Cited by 9 publications

(6 citation statements)

References 46 publications

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“…Silicosis is characterized by sustaining inflammatory responses and progressive pulmonary fibrosis [ 8 ]. Inhalation of crystalline silica could activate immune and non-immune cells, such as epithelial cells, fibroblasts and macrophages, which could release inflammatory cytokines and fibrotic cytokines, such as TGF-β1, CTGF, TNF-α and IL-6 [ 5 , 7 , 25 , 26 ]. Studies found that TNF-α and IL-6 were increased in the serum [ 27 ] and BALF [ 28 ] of patients with silicosis.…”

Section: Discussionmentioning

confidence: 99%

“…When crystalline silica are inhaled and then engulfed by alveolar macrophages, many pro-inflammatory and pro-fibrotic cytokines, such as transforming growth factor-β1 (TGF-β1) [ 4 ], connective tissue growth factor (CTGF) [ 5 ], tumour necrosis factor-α (TNF-α) [ 6 ] and interleukin-6 (IL-6) [ 7 ], are released to trigger inflammatory cell infiltration, followed by fibroblast proliferation and collagen deposition [ 8 ]. These findings suggest critical roles of TGF-β1, CTGF, TNF-α and IL-6 in silicosis.…”

Section: Introductionmentioning

confidence: 99%

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The significance of serum S100 calcium-binding protein A4 in silicosis

Zhang

Yuan

et al. 2022

BMC Pulm Med

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Background Silicosis is a chronic occupational pulmonary disease characterized by persistent inflammation and irreversible fibrosis. Considerable evidences now indicate that S100 calcium-binding protein A4 (S100A4) has been associated with fibrotic diseases. However, the role of S100A4 in silicosis is still unclear. Methods In this study, serum levels of S100A4, transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in patients with silicosis (n = 42) and control group (CG, n = 12) were measured by ELISA. S100A4 expression in lung tissues and primary alveolar macrophages (AMs) of mice with and without silicosis was detected by immunohistochemistry (IHC)/real-time PCR. The correlations between S100A4 and cytokines or lung function were assessed by Spearman's rank correlation analyses. Results Compared with CG, the levels of S100A4 were significantly increased in silicosis patients (70.84 (46.22, 102.46) ng/ml vs (49.84 (42.86, 60.02) ng/ml). The secretions of TGF-β1, CTGF, IL-6 and TNF-α in silicosis group were significantly higher than that in control group (p < 0.05). Serum S100A4 levels were positively correlated with TGF-β1 and IL-6, while were negatively correlated with lung function parameters including percentage of predicted forced vital capacity (FVC%pre), maximum vital capacity (Vcmax), deep inspiratory capacity (IC) and peak expiratory flow at 75% of vital capacity (PEF75). In receiver operating characteristic (ROC) analyses, S100A4 > 61.7 ng/ml had 63.4% sensitivity and 83.3% specificity for silicosis, and the area under the curve (AUC) was 0.707. Furthermore, immunostaining of lung tissues showed the accumulation of S100A4-positive cells in the areas of nodules of silicotic mice. The mRNA expression of S100A4 in the lung tissues and AMs of silicotic mice were significantly higher than controls. Conclusion These data suggested that increased S100A4 might contribute to the pathogenesis of silicosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The significance of serum S100 calcium-binding protein A4 in silicosis

Zhang

Yuan

et al. 2022

BMC Pulm Med

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“…AECII and activated fibroblasts secrete CTGF via autocrine and paracrine secretion, which contributes to the capacity of injured alveolar epithelial cells undergoing EMT to promote fibroblasts’ migration and proliferation [ 50 , 51 ]. The knockdown of the CTGF gene was shown to attenuate inflammatory responses induced by silica in bronchial epithelial cells [ 52 ].…”

Section: Ctgf Maintains the Pro-fibrotic Environment In Ipfmentioning

confidence: 99%

Connective Tissue Growth Factor in Idiopathic Pulmonary Fibrosis: Breaking the Bridge

Effendi

Nagano

2022

IJMS

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CTGF is upregulated in patients with idiopathic pulmonary fibrosis (IPF), characterized by the deposition of a pathological extracellular matrix (ECM). Additionally, many omics studies confirmed that aberrant cellular senescence-associated mitochondria dysfunction and metabolic reprogramming had been identified in different IPF lung cells (alveolar epithelial cells, alveolar endothelial cells, fibroblasts, and macrophages). Here, we reviewed the role of the CTGF in IPF lung cells to mediate anomalous senescence-related metabolic mechanisms that support the fibrotic environment in IPF.

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“…A recent study by Zhou et al (2019) associated the inflammatory process caused by exposure to silica with the inhibition of connective tissue growth factor (CTGF). The authors reported that exposure to silica particles increased the expression of the CTGF gene and several genes associated with inflammation.…”

Section: Occupational Exposure To Silica and Health Effectsmentioning

confidence: 99%

Occupational exposure to crystalline silica and peripheral biomarkers: An update

Peruzzi

Brucker

Bubols

et al. 2021

J of Applied Toxicology

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Peripheral biomarkers are important tools for detecting occupational exposures to prevent the onset and/or progression of diseases. Studies that reveal early peripheral biomarkers are highly important to preserve the health of workers and can potentially contribute to diagnosing and/or prognosing occupational pathologies. Exposure to crystalline silica is a problem in several workplaces because it increases the risk of chronic obstructive pulmonary disease (COPD), tuberculosis, cancer, and pulmonary fibrosis, clinically defined as silicosis. Silicosis is diagnosed by chest radiography and/or lung tomography in advanced stages when there is a severe loss of lung function. Peripheral biomarkers can help in diagnosing early changes prior to silicosis and represent a highly important technical‐scientific advance that is minimally invasive. This review aimed to investigate the biomarkers studied for evaluating occupational exposure to crystalline silica and to understand the recent advances in this area. Potential oxidative, inflammatory, and immunological biomarkers were reviewed, as well as routine biomarkers such as biochemical parameters. It was found that biomarkers of effect such as serum CC16 and l‐selectin levels could represent promising alternatives. Additionally, studies have shown that neopterin levels in urine and serum can be used to monitor worker exposure. However, further studies are needed that include a greater number of participants, different times of exposure to crystalline silica, and a combination of silicosis patients and healthy volunteers. Evaluating the concentration of crystalline silica in occupational environments, its impact on biomarkers of effect, and alterations in lung function could contribute to revealing early health alterations in workers in a more robust manner.

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The Role of CTGF in Inflammatory Responses Induced by Silica Particles in Human Bronchial Epithelial Cells

Cited by 9 publications

References 46 publications

The significance of serum S100 calcium-binding protein A4 in silicosis

The significance of serum S100 calcium-binding protein A4 in silicosis

Connective Tissue Growth Factor in Idiopathic Pulmonary Fibrosis: Breaking the Bridge

Occupational exposure to crystalline silica and peripheral biomarkers: An update

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