Fibroblasts that resist cigarette smoke-induced senescence acquire profibrotic phenotypes

Nobuhiro Kanaji, Hesham Basma, Amy Nelson, Maha Farid, Tadashi Sato, Masanori Nakanishi, Xingqi Wang, Joel Michalski, Ying Ji Li, Yoko Gunji, Carol Feghali-Bostwick, Xiangde Liu, Stephen I. Rennard

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

This study assessed the effect of extended exposure to cigarette smoke extract (CSE) on tissue repair functions in lung fibroblasts. Human fetal (HFL-1) and adult lung fibroblasts were exposed to CSE for 14 days. Senescence-associated β-galactosidase (SA β-gal) expression, cell proliferation, and tissue repair functions including chemotaxis and gel contraction were assessed. HFL-1 proliferation was inhibited by CSE and nearly half of the CSE-exposed cells were SA β-gal positive after 14 days exposure, whereas 33% of adult lung fibroblasts were SA β-gal positive in response to 10% CSE exposure. The SA β-gal-positive cells did not proliferate as indicated by bromodeoxyuridine incorporation. In contrast, cells negative for SA β-gal after CSE exposure proliferated faster than cells never exposed to CSE. These nonsenescent cells migrated more and contracted collagen gels more than control cells. CSE exposure stimulated TGF-β1production, and both inhibition of TGF-β receptor kinase and TGF-β1 siRNA blocked CSE modulation of fibroblast function. Extended exposure to CSE might induce two different fibroblast phenotypes, a senescent and a profibrotic phenotype. The fibroblasts that resist CSE-induced cellular senescence may contribute to the pathogenesis of idiopathic pulmonary fibrosis and could contribute to fibrotic lesions in chronic obstructive pulmonary disease acting through a TGF-β1-mediated pathway. In contrast, the senescent cells may contribute to the pathogenesis of emphysema.

Original languageEnglish (US)
Pages (from-to)L364-L373
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume307
Issue number5
DOIs
StatePublished - Sep 1 2014

Keywords

  • Fibroblast
  • Fibrotic phenotype
  • Senescence

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Kanaji, N., Basma, H., Nelson, A., Farid, M., Sato, T., Nakanishi, M., Wang, X., Michalski, J., Li, Y. J., Gunji, Y., Feghali-Bostwick, C., Liu, X., & Rennard, S. I. (2014). Fibroblasts that resist cigarette smoke-induced senescence acquire profibrotic phenotypes. American Journal of Physiology - Lung Cellular and Molecular Physiology, 307(5), L364-L373. https://doi.org/10.1152/ajplung.00041.2014