Fibroblasts that resist cigarette smoke-induced senescence acquire profibrotic phenotypes - PubMed (original) (raw)

. 2014 Sep 1;307(5):L364-73.

doi: 10.1152/ajplung.00041.2014. Epub 2014 Jul 11.

Hesham Basma 2, Amy Nelson 2, Maha Farid 2, Tadashi Sato 3, Masanori Nakanishi 4, Xingqi Wang 2, Joel Michalski 2, YingJi Li 5, Yoko Gunji 2, Carol Feghali-Bostwick 6, Xiangde Liu 2, Stephen I Rennard 7

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Fibroblasts that resist cigarette smoke-induced senescence acquire profibrotic phenotypes

Nobuhiro Kanaji et al. Am J Physiol Lung Cell Mol Physiol. 2014.

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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-β1 production, 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.

Keywords: fibroblast; fibrotic phenotype; senescence.

Copyright © 2014 the American Physiological Society.

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