IPF lung fibroblasts have a senescent phenotype

Diana Álvarez, Nayra Cárdenes, Jacobo Sellarés, Marta Bueno, Catherine Corey, Vidya Sagar Hanumanthu, Yating Peng, Hannah D’Cunha, John Sembrat, Mehdi Nouraie, Swaroop Shanker, Chandler Caufield, Sruti Shiva, Mary Armanios, Ana L. Mora, Mauricio Rojas

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanisms of aging that are involved in the development of idiopathic pulmonary fibrosis (IPF) are still unclear. Although it has been hypothesized that the proliferation and activation of human lung fibroblasts (hLFs) are essential in IPF, no studies have assessed how this process works in an aging lung. Our goal was to elucidate if there were age-related changes on primary hLFs isolated from IPF lungs compared with age-matched controls. We investigated several hallmarks of aging in hLFs from IPF patients and age-matched controls. IPF hLFs have increased cellular senescence with higher expression of β-galactosidase, p21, p16, p53, and cytokines related to the senescence-associated secretory phenotype (SASP) as well as decreased proliferation/apoptosis compared with age-matched controls. Additionally, we observed shorter telomeres, mitochondrial dysfunction, and upon transforming growth factor-β stimulation, increased markers of endoplasmic reticulum stress. Our data suggest that IPF hLFs develop senescence resulting in a decreased apoptosis and that the development of SASP may be an important contributor to the fibrotic process observed in IPF. These results might change the existing paradigm, which describes fibroblasts as aberrantly activated cells, to a cell with a senescence phenotype.

Original languageEnglish (US)
Pages (from-to)L1164-L1173
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume313
Issue number6
DOIs
StatePublished - Dec 2017

Keywords

  • Aging
  • Collagen
  • Fibroblasts
  • Idiopathic pulmonary fibrosis
  • Mitochondria
  • Senescence
  • TGF-β
  • Telomeres

ASJC Scopus subject areas

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

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