Cellular senescence mediates fibrotic pulmonary disease 

Nat Commun.8:14532, 2017

 

Speaker: Shang-Yi Lin (林尚儀)   Time: 13:00~14:00, Nov. 01, 2017

Commentator: Dr. Tang-Hsiu Huang (黃堂修老師)   Place: Room 601

 

Abstract:

Idiopathic pulmonary fibrosis (IPF) is a senile disease with progressive pulmonary interstitial fibrosis as a result of destruction of the lung parenchyma. When the lung is injured, it can undergo several self-repair stages, including fibroblast migration/proliferation/ activation, tissue remodeling and resolution phase1. However, in aging organisms, the ability of wound healing and fibrosis resolution are inadequate2, which leads to scar formation and fibrosis. Previous studies have shown that cellular senescence biomarkers were detected in human IPF lung3 and elimination of senescent cell restored lung function4. However, how senescent cells mediate IPF pathology and the effects of senescent cell removal are still largely unknown. In this study, first, the authors found that both fibroblasts and epithelial cells expressed senescent biomarker p16 and senescence-associated secretory phenotype (SASP) in IPF lung samples and the bleomycin-induced lung injury model. Furthermore, the secretome of senescent fibroblasts is profibrotic. Second, the authors treated a senolytic cocktail, dasatinib plus quercetin (DQ), to mice with bleomycin-induced lung injury. Senescent cell clearance by DQ treatment at the onset of pathogenesis reduced p16 levels and blunted increases of SASP factors which mitigated fibrotic lung disease. Thus, these results implicate that presence and activities of senescent cells may contribute to fibrotic lung disease. Removal of senescence cells may be a promising therapeutic strategy to improve pulmonary function and physical health.

 

References:

1. Wynn, T. A. Integrating mechanisms of pulmonary fibrosis. J. Exp. Med. 208, 1339-1350 (2011).

2. Hecker, L. et al. Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci. Transl. Med. 6, 231ra247 (2014).

3. Lomas, N. J. et al. Idiopathic pulmonary fibrosis: immunohistochemical analysis provides fresh insights into lung tissue remodelling with implications for novel prognostic markers. Int. J. Clin. Exp. Pathol. 5, 58-71 (2012).

4. Hashimoto, M. et al. Elimination of p19ARF-expressing cells enhances pulmonary function in mice. JCI Insight 1, e87732 (2016).