Cigarette Smoke Extract-Induced Oxidative Stress and Fibrosis-Related Genes Expression in Orbital Fibroblasts from Patients with Graves’ Ophthalmopathy

Cigarette smoking is the most important risk factor for the development or deterioration of Graves’ ophthalmopathy. Smoke-induced increased generation of reactive oxygen species may be involved. However, it remains to be clarified how orbital fibroblasts are affected by cigarette smoking. Our study demonstrated that Graves’ orbital fibroblasts have exaggerated response to cigarette smoke extract challenge along with increased oxidative stress, fibrosis-related genes expression, especially connective tissue growth factor, and intracellular levels of transforming growth factor-β1 and interleukin-1β. The findings obtained in this study provide some clues for the impact of cigarette smoking on Graves’ ophthalmopathy and offer a theoretical basis for the potential and rational use of antioxidants in treating Graves’ ophthalmopathy.

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Alteration of Connective Tissue Growth Factor (CTGF) Expression in Orbital Fibroblasts from Patients with Graves’ Ophthalmopathy

PLoS ONE ◽

10.1371/journal.pone.0143514 ◽

2015 ◽

Vol 10 (11) ◽

pp. e0143514 ◽

Cited By ~ 6

Author(s):

Chieh-Chih Tsai ◽

Shi-Bei Wu ◽

Pei-Chen Chang ◽

Yau-Huei Wei

Keyword(s):

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Tissue Growth ◽

Graves Ophthalmopathy ◽

Orbital Fibroblasts

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JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts

International Journal of Molecular Sciences ◽

10.3390/ijms22062952 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2952

Author(s):

Tzu-Yu Hou ◽

Shi-Bei Wu ◽

Hui-Chuan Kau ◽

Chieh-Chih Tsai

Keyword(s):

Growth Factor ◽

Transforming Growth Factor ◽

Mapk Pathway ◽

Transforming Growth Factor Β1 ◽

Tissue Growth ◽

Mitogen Activated Protein Kinase ◽

Tissue Inhibitors Of Metalloproteinases ◽

Western Blots ◽

Orbital Fibroblasts ◽

Tgf Β1

Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves’ ophthalmopathy (GO). However, the signaling pathways through which TGF-β1 activates Graves’ orbital fibroblasts remain unclear. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in TGF-β1-induced myofibroblast transdifferentiation in human Graves’ orbital fibroblasts. The MAPK pathway was assessed by measuring the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) by Western blots. The expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and fibronectin representing fibrogenesis was estimated. The activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) responsible for extracellular matrix (ECM) metabolism were analyzed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of the MAPK pathway. After treatment with TGF-β1, the phosphorylation levels of p38 and JNK, but not ERK, were increased. CTGF, α-SMA, and fibronectin, as well as TIMP-1 and TIMP-3, were upregulated, whereas the activities of MMP-2/-9 were inhibited. The effects of TGF-β1 on the expression of these factors were eliminated by p38 and JNK inhibitors. The results suggested that TGF-β1 could induce myofibroblast transdifferentiation in human Graves’ orbital fibroblasts through the p38 and JNK pathways.

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Pirfenidone mediates cigarette smoke extract induced inflammation and oxidative stress in vitro and in vivo

International Immunopharmacology ◽

10.1016/j.intimp.2021.107593 ◽

2021 ◽

Vol 96 ◽

pp. 107593

Author(s):

Yiming Ma ◽

Lijuan Luo ◽

Xiangming Liu ◽

Herui Li ◽

Zihang Zeng ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Cigarette Smoke Extract ◽

And Oxidative Stress

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Maternal Oxidative Stress, Placental Morphometry, and Fetal Growth in Diabetic Rats Exposed to Cigarette Smoke

Reproductive Sciences ◽

10.1177/1933719118815589 ◽

2018 ◽

Vol 26 (9) ◽

pp. 1287-1293 ◽

Cited By ~ 4

Author(s):

Yuri K. Sinzato ◽

Estela M. Bevilacqua ◽

Gustavo T. Volpato ◽

Rogelio E. Hernandez-Pando ◽

Marilza V. C. Rudge ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Fetal Growth ◽

Fetal Development ◽

Oxidative Stress Biomarkers ◽

Junctional Zone ◽

Pregnant Rats ◽

Stress Biomarkers ◽

Vascular Walls ◽

The Impact

The diabetic syndrome affects pregnancy, contributing to placental functional and structural disruptions and impaired fetal development, with many reports indicating tobacco-associated morbidity and perinatal mortality. In our study, an experimental rat model of diabetes and cigarette smoke exposure in pregnant rats was used to determine the impact of the combination of diabetes and exposure to cigarette smoke during pregnancy on maternal oxidative stress biomarkers and placental and fetal development. Diabetes was induced by streptozotocin, and dams were exposed to cigarette smoke by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Four groups of dams were studied: nondiabetic (C, control) and diabetic (D) exposed to filtered air and nondiabetic (CS) and diabetic (DS) exposed to cigarette smoke prior to and during pregnancy. Maternal oxidative stress biomarkers, placental morphology, and fetal growth were determined close to term. The combination of diabetes and cigarette smoke resulted in elevated maternal blood glucose levels and increased number of small fetuses. Placentas from the DS group showed increased junctional zone and decreased labyrinthine area. The morphological alterations were characterized by extensive vascular congestion, thickness, and hyalinization of the vascular walls, numerous decidual cells with abundant glycogen, and macrophages with cytoplasmic inclusions of hemosiderin. Additionally, they showed increased glycogen accumulation and junctional zone structural derangement with ectopic giant cells. No alterations were observed in maternal oxidative stress status. Thus, our result suggests that diabetes makes pregnant rats more susceptible to the adverse effects of exposure to cigarette smoke on placental morphometry and fetal growth.

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Vascular Endothelial Growth Factor Reduced and Connective Tissue Growth Factor Induced by Triamcinolone in ARPE19 Cells under Oxidative Stress

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.04-0761 ◽

2005 ◽

Vol 46 (3) ◽

pp. 1062 ◽

Cited By ~ 58

Author(s):

Satoshi Matsuda ◽

Fumi Gomi ◽

Yusuke Oshima ◽

Masaya Tohyama ◽

Yasuo Tano

Keyword(s):

Oxidative Stress ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Tissue Growth ◽

Vascular Endothelial ◽

Endothelial Growth Factor

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Exposure to the gut microbiota from cigarette smoke-exposed mice exacerbates cigarette smoke extract-induced inflammation in zebrafish larvae

10.1101/2021.09.20.461170 ◽

2021 ◽

Author(s):

Simone Morris ◽

Kathryn Wright ◽

Vamshikrishna Malyla ◽

Warwick J Britton ◽

Philip M Hansbro ◽

...

Keyword(s):

Cigarette Smoking ◽

Gut Microbiota ◽

Cigarette Smoke ◽

Cigarette Smoke Extract ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Zebrafish Larvae ◽

Modifying Factors ◽

Physiological Processes ◽

Inflammatory Phenotype

AbstractCigarette smoke (CS)-induced inflammation leads to a range of diseases including chronic obstructive pulmonary disease and cancer. Environmental factors including gut microbiota make up are major modifying factors that determine the severity of cigarette smoke-induced pathology. Adult zebrafish display increased inflammatory cytokine transcription when exposed to cigarette smoke extract (CSE) but incongruously do not produce a mucosal leukocytic inflammation phenotype. Zebrafish embryos and larvae have been used to model the effects of cigarette smoking on a range of physiological processes and offer an amenable platform for screening modifiers of cigarette smoke-induced pathologies. Here we exposed zebrafish larvae to CSE and showed that it was toxic and we characterised a CSE-induced leukocytic inflammatory phenotype with increased neutrophilic and macrophage responses. The CSE-induced phenotype was exacerbated by co-exposure to microbiota from the faeces of CS-exposed mice, but not control mice. Microbiota could be recovered from the gut of zebrafish and studied in isolation. This demonstrates the utility of the zebrafish-CSE exposure platform for identifying environmental modifiers of cigarette smoking-associated pathology and demonstrates that the CS-exposed mouse gut microbiota potentiates the inflammatory effects of CSE across host species.

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