Copper as the most likely pathogenic divergence factor between lung fibrosis and emphysema

Janssen, Rob; Brouwer, Bart de; Thüsen, Jan H. von der; Wouters, Emiel F.M.

doi:10.1016/j.mehy.2018.08.003

Cited by 24 publications

(23 citation statements)

References 40 publications

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“…This free radical can promote inflammasome activation and induce astrocyte apoptosis in Alzheimer’s disease 11 . Recently, increasing epidemiological and experimental data have shown that copper levels increase greatly in sputum or lung tissues of patients with various chronic pulmonary diseases, including chronic asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and pulmonary fibrosis 12–14 . Undoubtedly, abnormal accumulation of copper accelerates the phenotype of such diseases.…”

Section: Introductionmentioning

confidence: 99%

Inflammation accelerates copper‐mediated cytotoxicity through induction of six‐transmembrane epithelial antigens of prostate 4 expression

Jiang

Xue

et al. 2021

Immunol. Cell Biol.

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Copper is an essential trace metal, but imbalance in copper homeostasis can induce oxidative damage. Inflammation is a fundamental element of various pulmonary diseases. Although a positive relationship between copper and chronic pulmonary diseases has been reported, the underlying reasons are still not clear. The copper level in the sputum of patients with various pulmonary diseases was measured. An inflammatory model was established to evaluate the impact of inflammation on copper uptake in the lung. We found that the level of sputum copper was increased in patients with various pulmonary diseases, especially chronic obstructive pulmonary disease and asthma. Then, we confirmed that mice with pulmonary inflammation were susceptible to copper‐mediated oxidative damage because of copper overload in lung tissue. Further investigation demonstrated that interleukin (IL)‐17 and tumor necrosis factor (TNF)‐α exerted synergistic effects in airway epithelial cells by upregulating the expression of six‐transmembrane epithelial antigens of prostate 4 (STEAP4), a metalloreductase that reduces extracellular copper ions from the cupric state to the cuprous state and facilitates copper uptake. Inhibition of STEAP4 decreased the copper uptake of cells and inhibited copper‐mediated oxidative damage. Moreover, we demonstrated that the upregulation of STEAP4 by IL‐17 and TNF‐α was largely dependent on TNF receptor‐associated factor 4 (TRAF4). Traf4−/− mice were resistant to copper‐mediated oxidative damage. Our data suggest a novel IL‐17/TNF‐α–TRAF4–STEAP4 axis that regulates copper homeostasis.

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Section: Introductionmentioning

confidence: 99%

Inflammation accelerates copper‐mediated cytotoxicity through induction of six‐transmembrane epithelial antigens of prostate 4 expression

Jiang

Xue

et al. 2021

Immunol. Cell Biol.

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“…In addition, TE, a soluble precursor of elastin and also one of the powerful members of the ECMs, was believed as pro-fibrosis factors. Previous studies have indicated that the expression of TE was significantly increased in asbestos-induced airway fibrosis in rats and in fibrotic tissues such as skin white lines, fine-line scars, hypertrophic scars and keloids, becoming closely correlated with pulmonary fibrosis and skin fibrosis [20][21][22].Moreover, MFAP4 participate in the assembly of elastin together with TE and the two proteins were both up-regulated in liver fibrosis and cirrhosis, and can serve as a biomarker of liver fibrosis [14,17,23]. In liver fibrosis, TE acts directly on fibroblasts and inflammatory cells, and promotes angiogenesis, thus promoting the development of fibrosis [33].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the expression level of MFAP4 protein was slightly increased in the early-stage (n = 13, p = 0.0015) and mid-stage (n = 26, p = 0.0001) and significantly increased in the late-stage (n = 21, p < 0.0001). In previous research, interestingly, we found that TE and MFAP4 participate jointly in elastin assembly and are closely related to the progression of plenty of fibrotic diseases [14,17,21,25]. However, it is worth noting that the expression of TE protein at different OSF stages is unexplored.…”

Section: The Excessive Expression Of Mfap4 and Te Proteins Is Involved In The Progressing Of Osfmentioning

confidence: 92%

“…And TE protein is excreted by fibroblasts and vascular smooth muscle cells (VSMC) [18,19]. Moreover, up-regulated TE protein is involved in the process of fibrosis through influencing on fibroblasts, inflammatory cells and angiogenesis in skin, lung and liver fibrosis [20][21][22], [14,23]. However, the expression of TE protein and the correlation between MFAP4 and TE in the development of OSF remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Pathological Investigations And Correlation Research of Microfibrillar-Associated Protein 4 And Tropoelastin In Oral Submucous Fibrosis

Liu

Gou

Feng

2021

Preprint

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Background: Oral submucous fibrosis (OSF), distinguished by abnormal collagen deposition, is a precancerous disorder with 7%-30% of malignant transformation and rising global prevalence. However, the precise pathogenesis and effective treatment still remains elusive and controversial despite superfluity of literature. Therefore, it is extremely necessary and significant to explore the clinicopathological characteristics and potential markers for diagnosis and prognosis of OSF. Here, the objective of this research is to evaluate the influence and correlation of Microfibrillar-associated protein 4 [MFAP4] and tropoelastin [TE] on the development of OSF patients. Material and Methods: Classic clinicopathological factors, HE and Masson trichome staining, immunohistochemical characteristics and the correlation (MFAP4 and TE) were recorded and compared among different stages of OSF cases (n = 60) and among those normal individuals (n = 10). Then, the comparison using Student's t test, ANOVA analysis, the chi-square test for categorical variables was conducted in clinicopathological characteristics and the expression level of MFAP4 and TE between the patients' and normal tissue. The correlation analysis of MFAP4 and TE were assessed via means of Pearson's correlation test and linear regression. Results: MFAP4 and TE proteins are upregulated and even increasing gradually in varying grades of OSF patients relative to the normal cases. Furthermore, statistical analyses yielded that the expression level of MFAP4 was positively associated with TE, and the Pearson correlation coefficient was 0.3781 (p = 0.0048). Clinically, we found that OSF affected more male than female with a ratio of 29: 1. The age range was 16-60 years, and the mean age was 36.25 ± 10.25 years old. Moreover, the positive expression rate of MFAP4 and TE in patients less than 40 years old is higher than that of those over 40 years old. Meanwhile, all OSF cases had chewed areca nut, with 51.67% smoking tobacco. Conclusions: Our study elucidates that the accumulation of MFAP4 and TE proteins may play a vitally important effect in the occurrence and development of OSF and has a hope to become a promising candidate molecular for prevention, diagnosis, and treatment strategies of OSF in the future.

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“…ATPase copper-transporting alpha (ATP7A) and ATPase copper-transporting beta (ATP7B) are key players in copper homeostasis being required for copper delivery to the secretory pathway and for efflux of excess copper from the cell. Deregulation of this delicate balance that maintains copper homeostasis has been associated with The aim of the present review is to provide a global overview on the main different chelation therapy approaches which have been evaluated for the treatment of the diseases in which copper imbalance has a key role in the onset of the pathology, including genetic diseases of copper metabolism such as Wilson's diseases [8], neurodegenerative diseases such as Alzheimer's and Parkinson's diseases [14], idiopathic pulmonary fibrosis [15], diabetes [16], and different forms of cancer [17].…”

Section: Introductionmentioning

confidence: 99%

Current Biomedical Use of Copper Chelation Therapy

Baldari

Rocco

Toietta

2020

IJMS

124

105

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Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson’s syndrome, in neurological and neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.

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Copper as the most likely pathogenic divergence factor between lung fibrosis and emphysema

Cited by 24 publications

References 40 publications

Inflammation accelerates copper‐mediated cytotoxicity through induction of six‐transmembrane epithelial antigens of prostate 4 expression

Inflammation accelerates copper‐mediated cytotoxicity through induction of six‐transmembrane epithelial antigens of prostate 4 expression

Pathological Investigations And Correlation Research of Microfibrillar-Associated Protein 4 And Tropoelastin In Oral Submucous Fibrosis

Current Biomedical Use of Copper Chelation Therapy

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