Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing

Pharmaceutics

Glen Westall¹  Jade Jaffar¹  CeciliaM. Prêle²  StevenE. Mutsaers²  ChristopherL. Grainge³  KajE. C. Blokland⁴  DavidW. Waters⁴  DarrylA. Knight⁴  Michael Schuliga⁴  Jane Read⁴  JanetteK. Burgess⁵  SimonD. Pouwels⁶ 

[1] Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Prahran, Vic 3004, Australia;Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences University of Western Australia, Crawley, WA 6009, Australia;National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis, Camperdown, NSW 2050, Australia;School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia;University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, 9713 GZ Groningen, The Netherlands;University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, 9713 GZ Groningen, The Netherlands;

关键词: senescence;    fibroblasts;    alveolar epithelial cell;    fibrosis;    aberrant repair;    cell-cycle inhibition;   

DOI  :  10.3390/pharmaceutics12040389

来源: DOAJ

【 摘 要 】

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive accumulation of lung fibroblasts (LFs) and collagen in the lung parenchyma. The mechanisms that underlie IPF pathophysiology are thought to reflect repeated alveolar epithelial injury leading to an aberrant wound repair response. Recent work has shown that IPF-LFs display increased characteristics of senescence including growth arrest and a senescence-associated secretory phenotype (SASP) suggesting that senescent LFs contribute to dysfunctional wound repair process. Here, we investigated the influence of senescent LFs on alveolar epithelial cell repair responses in a co-culture system. Alveolar epithelial cell proliferation was attenuated when in co-culture with cells or conditioned media from, senescence-induced control LFs or IPF-LFs. Cell-cycle analyses showed that a larger number of epithelial cells were arrested in G2/M phase when co-cultured with IPF-LFs, than in monoculture. Paradoxically, the presence of LFs resulted in increased A549 migration after mechanical injury. Our data suggest that senescent LFs may contribute to aberrant re-epithelialization by inhibiting proliferation in IPF.

【 授权许可】

Unknown