Fibroblast senescence in the pathology of idiopathic pulmonary fibrosis

David W Waters, Kaj E C Blokland, Prabuddha S Pathinayake, Janette K Burgess, Steven E Mutsaers, Cecilia M Prêle, Michael Schuliga, Christopher L Grainge, Darryl A Knight

Research output: Contribution to journalReview article

53 Citations (Scopus)

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause with a median survival of only 3 years. Little is known about the mechanisms that precede the excessive collagen deposition seen in IPF, but cellular senescence has been strongly implicated in disease pathology. Senescence is a state of irreversible cell cycle arrest accompanied by an abnormal secretory profile and is thought to play a critical role in both development and wound repair. Normally, once a senescent cell has contributed to wound repair it is promptly removed from the environment via infiltrating immune cells. However, if immune clearance fails, the persistence of senescent cells is thought to drive disease pathology through their altered secretory profile. One of the major cell types involved in wound healing are fibroblasts, and senescent fibroblasts have been identified in the lungs of IPF patients and in fibroblast cultures from IPF lungs. The question of what is driving abnormally high numbers of fibroblasts into senescence remains unanswered. The transcription factor STAT3 plays a role in a myriad of processes including cell cycle progression, gene transcription as well as mitochondrial respiration, all of which are dysregulated during senescence. Activation of STAT3 has previously been shown to correlate with IPF progression and therefore is a potential molecular target to modify early-stage senescence and restore normal fibroblast function. This review summarises what is currently known about fibroblast senescence in IPF and how STAT3 may contribute to this phenotype.

Original languageEnglish
Pages (from-to)L162-L172
Number of pages11
JournalAmerican Journal of Physiology: Lung Cellular and Molecular Physiology
Volume315
Issue number2
DOIs
Publication statusPublished - Aug 2018

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