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Zhou S.,Hefei Prevention and Treatment Center for Occupational Diseases | Zhou S.,Anhui Medical University | Li M.,Anhui Medical University | Zeng D.,Soochow University of China | And 5 more authors.
Cellular Physiology and Biochemistry

Objective: Polymorphisms located at microRNA (miRNA) binding sites may interfere with the miRNA/mRNA interaction. The objective of this study was to identify the association between a single nucleotide polymorphism (774 T>C) in 3'-untranslated region (3'-UTR) of Epithelial Growth Factor Receptor (EGFR) and development of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) as well as to explore the molecular mechanism. Methods and Results: In this study, we validated EGFR as a target of miR-214 in pulmonary artery smooth muscle cell (PASMC), which was further confirmed by the observation that exogenous overexpression of miR-214 significantly downregulated the expression of EGFR in the PASMCs genotyped as TT or TC, but not in CC group. Meanwhile, we found COPD patients with CC genotype had significantly higher risk for PH (OR = 1.965, p = 0.0095), compared with TT and TC genotypes,. Additionally, the PASMCs were isolated from 72 COPD patients, with which miR-214 and EGFR expression levels were determined, and we found that miR-214 level was comparable between each genotype group, the concentration of EGFR in CC genotype group was significantly higher than in TT or TC genotype group. Conclusion: Our study confirmed that EGFR 3'UTR 774 T>C polymorphism interfered with miRNA/mRNA interaction, and showed that the minor allele was associated with an elevated risk for development of PH in COPD. © 2015 S. Karger AG, Basel. Source

Wang R.,Anhui Medical University | Zhou S.-J.,Anhui Medical University | Zhou S.-J.,Hefei Prevention and Treatment Center for Occupational Diseases | Zeng D.-X.,Soochow University of China | And 5 more authors.
Gene Therapy

Pulmonary hypertension is a life-threatening medical condition, and a growing body of evidence shows that the expression of connective tissue growth factor (CTGF) is significantly associated with its pathogenesis, making it an attractive therapeutic target. Our earlier work revealed that plasmid-based CTGF-specific short hairpin RNA (shRNA) could attenuate pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling in rats exposed to cigarette smoke. In this study, we explored the therapeutic role of this shRNA plasmid in the treatment of monocrotaline-induced pulmonary vascular remodeling in rats, and demonstrated that the upregulation of CTGF in PASMCs following a single injection of monocrotaline could be attenuated by administration of the shRNA. Accordingly, this shRNA was found to repress monocrotaline-induced pulmonary vascular remodeling, as evidenced by its ability to reduce the percentage of muscularized vessels and the wall thickness of pulmonary vessels. We concluded that plasmid-based shRNA against CTGF attenuated pulmonary vascular remodeling in monocrotaline-treated rats. CTGF might be a potential target for the treatment of pulmonary vascular remodeling and pulmonary hypertension. © 2014 Macmillan Publishers Limited All rights reserved. Source

Zhou S.-J.,Hefei Prevention and Treatment Center for Occupational Diseases | Zhou S.-J.,Anhui Medical University | Li M.,Anhui Medical University | Zeng D.-X.,Soochow University of China | And 5 more authors.
Scientific Reports

Cigarette smoking contributes to the development of pulmonary hypertension (PH) complicated with chronic obstructive pulmonary disease (COPD), and the pulmonary vascular remodeling, the structural basis of PH, could be attributed to abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs).In this study, morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than in nonsmokers. In addition, we determined the expression patterns of connective tissue growth factor (CTGF) and cyclin D1 in PASMCs harvested from smokers with normal lung function or mild to moderate COPD, finding that the expression levels of CTGF and cyclin D1 were significantly increased in smoker group and COPD group. In vitro experiment showed that the expression of CTGF, cyclin D1 and E2F were signficantly increased in human PASMCs (HPASMCs) treated with 2% cigarette smoke extract (CSE), and two CTGF siRNAs with different mRNA hits successfully attenuated the upregulated cyclin D1 and E2F, and significantly restored the CSE-induced proliferation of HPASMCs by causing cell cycle arrest in G0. These findings suggest that CTGF may contribute to the pathogenesis of abnormal proliferation of HPASMCs by promoting the expression of its downstream effectors in smokers with or without COPD. Source

Wang R.,Anhui Medical University | Yang X.,Anhui Medical University | Zhou S.,Hefei Prevention and Treatment Center for Occupational Diseases | Sun G.,Anhui Medical University
Experimental and Therapeutic Medicine

The aim of this study was to investigate the clinical characteristics, diagnosis and treatment of anti-neutrophil cytoplasmic antibody (ANCA)-negative microscopic polyangiitis (MPA). We described the case of a patient with ANCA‑negative MPA and conducted analyses and a review of the relevant literature. Based on the collected data, the epidemiology, diagnosis and treatment of ANCA‑negative MPA were discussed. The patient, a 69‑year‑old male, was initially diagnosed with pneumonia and interstitial lung disease (ILD) based on his clinical symptoms. The patient was ANCA‑negative. The follow‑up and consultations with the relevant departments after the ANCA testing led to a diagnosis of MPA being considered. The administration of glucocorticoids and immunosuppressant drugs was found to improve the symptoms of the patient. The clinical symptoms of MPA are unspecific. The majority of MPA cases are ANCA‑positive, but misdiagnosis should be considered as a possibility in ANCA‑negative cases. When patients are suspected to have MPA, therefore, ANCA tests should be immediately performed. Test results should be analyzed for the early diagnosis of MPA in order to enable the provision of immediate treatment, improve patient prognosis and reduce mortality rate. © 2015, Spandidos Publications. All rights reserved. Source

Wang R.,Anhui Medical University | Li M.,Anhui Medical University | Zhou S.,Anhui Medical University | Zhou S.,Hefei Prevention and Treatment Center for Occupational Diseases | And 4 more authors.
International Journal of COPD

Objective: To evaluate the effect of a single nucleotide polymorphism (rs2910164) in the miR-146a precursor on the expression level of miR-146a, cyclooxygenase-2 (COX2), and production of prostaglandin E2 (PGE2) in lung tissue harvested from smokers with chronic obstructive pulmonary disease, as well as the lung function and disease stages from the same patient population. Methods and results: One-hundred and sixty-eight smokers with diagnosed chronic obstructive pulmonary disease were recruited. The patients were genotyped for rs2910164 polymorphism using Sanger sequencing, and their lung function/disease stages were evaluated following Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Meanwhile, messenger ribonucleic acid and protein expression levels of miR-146a and COX2 as well as PGE2 production were determined in 66 lung tissue samples collected in the patients who received surgical treatment. We confirmed that COX2 is a validated target of miR-146a in human fibroblast cells, and identified the differential expression patterns of miR-146a and COX2 in each rs2910164 genotype group. We observed a significant association between rs2910164 in miR-146a and the levels of either COX2 or PGE2 using real-time polymerase chain reaction and Western blot. Consistently, we were able to demonstrate that the rs2910164 single nucleotide polymorphism has a functional effect on the baseline lung function in the study population. Conclusion: In the present study, the rs2910164 CC and GC genotype was found to be associated with an improved lung function and milder disease stages, at least partially, mediated by its ability to increase in COX2 expression and PGE2 production. © 2015 Wang et al. Source

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