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Cigarette smoke-induced alveolar epithelial-mesenchymal transition is mediated by Rac1 activation.
Shen, Hui-juan; Sun, Yan-hong; Zhang, Shui-juan; Jiang, Jun-xia; Dong, Xin-wei; Jia, Yong-liang; Shen, Jian; Guan, Yan; Zhang, Lin-hui; Li, Fen-fen; Lin, Xi-xi; Wu, Xi-mei; Xie, Qiang-min; Yan, Xiao-feng.
Afiliación
  • Shen HJ; The Second Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Sun YH; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Zhang SJ; Pharmacy College of Zhejiang Chinese Medical University, Hangzhou 310053, China.
  • Jiang JX; The Second Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Dong XW; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Jia YL; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Shen J; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Guan Y; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Zhang LH; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Li FF; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Lin XX; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Wu XM; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
  • Xie QM; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China; Laboratory Animal Center of Zhejiang University, Hangzhou 310058, China. Electronic address: xieqm@zju.edu.cn.
  • Yan XF; The Second Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China. Electronic address: yanxiaofeng0804@sina.com.
Biochim Biophys Acta ; 1840(6): 1838-49, 2014 Jun.
Article en En | MEDLINE | ID: mdl-24508121
ABSTRACT

BACKGROUND:

Epithelial-mesenchymal transition (EMT) is the major pathophysiological process in lung fibrosis observed in chronic obstructive pulmonary disease (COPD) and lung cancer. Smoking is a risk factor for developing EMT, yet the mechanism remains largely unknown. In this study, we investigated the role of Rac1 in cigarette smoke (CS) induced EMT.

METHODS:

EMT was induced in mice and pulmonary epithelial cells by exposure of CS and cigarette smoke extract (CSE) respectively.

RESULTS:

Treatment of pulmonary epithelial cells with CSE elevated Rac1 expression associated with increased TGF-ß1 release. Blocking TGF-ß pathway restrained CSE-induced changes in EMT-related markers. Pharmacological inhibition or knockdown of Rac1 decreased the CSE exposure induced TGF-ß1 release and ameliorated CSE-induced EMT. In CS-exposed mice, pharmacological inhibition of Rac1 reduced TGF-ß1 release and prevented aberrations in expression of EMT markers, suggesting that Rac1 is a critical signaling molecule for induction of CS-stimulated EMT. Furthermore, Rac1 inhibition or knockdown abrogated CSE-induced Smad2 and Akt (PKB, protein kinase B) activation in pulmonary epithelial cells. Inhibition of Smad2, PI3K (phosphatidylinositol 3-kinase) or Akt suppressed CSE-induced changes in epithelial and mesenchymal marker expression. CONCLUSIONS AND GENERAL

SIGNIFICANCE:

Altogether, these data suggest that CS initiates EMT through Rac1/Smad2 and Rac1/PI3K/Akt signaling pathway. Our data provide new insights into the fundamental basis of EMT and suggest a possible new course of therapy for COPD and lung cancer.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Alveolos Pulmonares / Humo / Nicotiana / Neuropéptidos / Proteína de Unión al GTP rac1 / Transición Epitelial-Mesenquimal Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Biochim Biophys Acta Año: 2014 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Alveolos Pulmonares / Humo / Nicotiana / Neuropéptidos / Proteína de Unión al GTP rac1 / Transición Epitelial-Mesenquimal Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Biochim Biophys Acta Año: 2014 Tipo del documento: Article País de afiliación: China