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LATE-BREAKING ABSTRACT: miR-877 and its target protein HDAC6 are involved in airway inflammation

Haozhong Lu, Jianrong Xu, Zhihua Yu, Juan Li, Yu Qiu, Wenhui Zhang, Yongyao Cui
European Respiratory Journal 2015 46: PA4360; DOI: 10.1183/13993003.congress-2015.PA4360
Haozhong Lu
Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Jianrong Xu
Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Zhihua Yu
Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Juan Li
Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Yu Qiu
Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Wenhui Zhang
Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Yongyao Cui
Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Abstract

Background: Several pathophysiological and molecular mechanisms including epigenetics have been shown to participate in the etiology of chronic obstructive pulmonary disease (COPD).

Aims and objectives: This study was aimed to 1) explore the role of miR-877 and 2) to determine its target proteins in airway inflammation related to COPD.

Methods: miRNA expression and their target proteins in cell lines and lung tissues from rat with airway inflammation were measured by quantitative real-time PCR, western blotting and ELISA.

Results: miR-877 was identified to be decreased in miRNA array analysis of NR8383 cells treated with LPS, which was further validated through real-time PCR. HDAC6, a predicted miR-877 target, was significantly up-regulated in NR8383 cells treated with LPS. Moreover, IL-6 and IL-8 production was increased concomitantly and such effect could be ablated by pretreatment with a HDAC6 specific inhibitor or by addition of buthioninesulfoximine (BSO), a specific inhibitor of GSH synthesis. Overexpression of miR-877 decreased HDAC6 expression and production of IL-6 and IL-8. In addition, long-term treatment of rat with cigarette smokes (CS), an airway inflammation model, also led to down-regulated miR-877 expression, which was accompanied by up-regulated HDAC6 expression and subsequent IL-8 and IL-6 secretion. Furthermore, treatment with carbocysteine (S-CMC), an anti-oxidant and mucolytic agent which produces GSH, significantly decreased miR-877 target protein HDAC6 expression as well as the secretion of IL-6 and IL-8.

Conclusions: miR-877 and its target protein HDAC6 played a key role in the airway inflammatory responses. LPS/CS-induced epigenetic changes could be modulated by S-CMC through GSH.

  • COPD - mechanism
  • Genetics
  • Treatments
  • Copyright ©ERS 2015
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LATE-BREAKING ABSTRACT: miR-877 and its target protein HDAC6 are involved in airway inflammation
Haozhong Lu, Jianrong Xu, Zhihua Yu, Juan Li, Yu Qiu, Wenhui Zhang, Yongyao Cui
European Respiratory Journal Sep 2015, 46 (suppl 59) PA4360; DOI: 10.1183/13993003.congress-2015.PA4360

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LATE-BREAKING ABSTRACT: miR-877 and its target protein HDAC6 are involved in airway inflammation
Haozhong Lu, Jianrong Xu, Zhihua Yu, Juan Li, Yu Qiu, Wenhui Zhang, Yongyao Cui
European Respiratory Journal Sep 2015, 46 (suppl 59) PA4360; DOI: 10.1183/13993003.congress-2015.PA4360
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