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Connective Tissue Growth Factor Promotes Pulmonary Epithelial Cell Senescence and Is Associated with COPD Severity.
Jang, Jun-Ho; Chand, Hitendra S; Bruse, Shannon; Doyle-Eisele, Melanie; Royer, Christopher; McDonald, Jacob; Qualls, Clifford; Klingelhutz, Aloysius J; Lin, Yong; Mallampalli, Rama; Tesfaigzi, Yohannes; Nyunoya, Toru.
Afiliación
  • Jang JH; a Department of Medicine , University of Pittsburgh , Pittsburgh , PA , USA.
  • Chand HS; b VA Pittsburgh Healthcare System , Pittsburgh , PA , USA.
  • Bruse S; c Department of Immunology , Herbert Wertheim College of Medicine, Florida International University Miami , Miami , FL , USA.
  • Doyle-Eisele M; d Regeneron Genetics Center , Tarrytown , NY , USA.
  • Royer C; e COPD Program, Lovelace Respiratory Research Institute , Albuquerque , NM , USA.
  • McDonald J; e COPD Program, Lovelace Respiratory Research Institute , Albuquerque , NM , USA.
  • Qualls C; e COPD Program, Lovelace Respiratory Research Institute , Albuquerque , NM , USA.
  • Klingelhutz AJ; f Biomedical Research Institute of New Mexico.
  • Lin Y; g Department of Microbiology , University of Iowa, Roy J. and Lucille A. Carver College of Medicine , Iowa City , IA , USA.
  • Mallampalli R; e COPD Program, Lovelace Respiratory Research Institute , Albuquerque , NM , USA.
  • Tesfaigzi Y; a Department of Medicine , University of Pittsburgh , Pittsburgh , PA , USA.
  • Nyunoya T; b VA Pittsburgh Healthcare System , Pittsburgh , PA , USA.
COPD ; 14(2): 228-237, 2017 Apr.
Article en En | MEDLINE | ID: mdl-28026993
The purpose of this study was to determine whether expression of connective tissue growth factor (CTGF) protein in chronic obstructive pulmonary disease (COPD) is consistent in humans and animal models of COPD and to investigate the role of this protein in lung epithelial cells. CTGF in lung epithelial cells of ex-smokers with COPD was compared with ex-smokers without COPD by immunofluorescence. A total of twenty C57Bl/6 mice and sixteen non-human primates (NHPs) were exposed to cigarette smoke (CS) for 4 weeks. Ten mice of these CS-exposed mice and eight of the CS-exposed NHPs were infected with H3N2 influenza A virus (IAV), while the remaining ten mice and eight NHPs were mock-infected with vehicle as control. Both mRNA and protein expression of CTGF in lung epithelial cells of mice and NHPs were determined. The effects of CTGF overexpression on cell proliferation, p16 protein, and senescence-associated ß-galactosidase (SA-ß-gal) activity were examined in cultured human bronchial epithelial cells (HBECs). In humans, CTGF expression increased with increasing COPD severity. We found that protein expression of CTGF was upregulated in lung epithelial cells in both mice and NHPs exposed to CS and infected with IAV compared to those exposed to CS only. When overexpressed in HBECs, CTGF accelerated cellular senescence accompanied by p16 accumulation. Both CTGF and p16 protein expression in lung epithelia are positively associated with the severity of COPD in ex-smokers. These findings show that CTGF is consistently expressed in epithelial cells of COPD lungs. By accelerating lung epithelial senescence, CTGF may block regeneration relative to epithelial cell loss and lead to emphysema.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Senescencia Celular / Mucosa Respiratoria / Enfermedad Pulmonar Obstructiva Crónica / Células Epiteliales / Factor de Crecimiento del Tejido Conjuntivo / Fumar Cigarrillos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Aged / Animals / Female / Humans / Middle aged Idioma: En Revista: COPD Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Senescencia Celular / Mucosa Respiratoria / Enfermedad Pulmonar Obstructiva Crónica / Células Epiteliales / Factor de Crecimiento del Tejido Conjuntivo / Fumar Cigarrillos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Aged / Animals / Female / Humans / Middle aged Idioma: En Revista: COPD Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido