Cellular senescence mediates fibrotic pulmonary disease

Schafer, Marissa; White, Thomas A.; Iijima, Koji; Haak, Andrew J.; Ligresti, Giovanni; Atkinson, Elizabeth J.; Oberg, Ann L.; Birch, Jodie; Salmonowicz, Hanna; Zhu, Yi; Mazula, Daniel L.; Brooks, Robert W.; Fuhrmann‐Stroissnigg, Heike; Pirtskhalava, Tamar; Prakash, Y. S.; Tchkonia, Tamar; Robbins, Paul D.; Aubry, Marie Christine; Passos, João F.; Kirkland, James L.; Tschumperlin, Daniel J.; Kita, Hirohito; LeBrasseur, Nathan K.

doi:10.1038/ncomms14532

articleNature CommunicationsFeb 23, 2017GOLD OA

Cellular senescence mediates fibrotic pulmonary disease

MSMarissa Schafer TAThomas A. White KIKoji Iijima AJAndrew J. Haak GLGiovanni Ligresti

Mayo Clinic · Mayo Clinic in Florida · +3 more institutions

PubMed

Indexed incrossrefdoajpubmed

Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF lung tissue and senescent cell deletion rejuvenates pulmonary health in aged mice. Whether and how senescent cells regulate IPF or if their removal may be an efficacious intervention strategy is unknown. Here we demonstrate elevated abundance of senescence biomarkers in IPF lung, with p16 expression increasing with disease severity. We show that the secretome of senescent fibroblasts, which are selectively killed by a senolytic cocktail, dasatinib plus quercetin (DQ), is fibrogenic. Leveraging the bleomycin-injury IPF…

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Topics & keywords

Topics

Keywords

Idiopathic pulmonary fibrosis
Senescence
Pulmonary fibrosis
Bleomycin
Lung
Fibrosis
Medicine
Disease

UN Sustainable Development Goals

Good health and well-being

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