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Am J Physiol Lung Cell Mol Physiol. 2018 Aug 1;315(2):L162-L172. doi: 10.1152/ajplung.00037.2018. Epub 2018 Apr 26.

Fibroblast senescence in the pathology of idiopathic pulmonary fibrosis.

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School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales , Australia.
Faculty of Health and Medicine, University of Newcastle , Callaghan , Australia.
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen Research Institute for Asthma and COPD , Groningen , The Netherlands.
School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales , Australia.
Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, University of Western Australia , Nedlands, Western Australia , Australia.
Institute for Respiratory Health, University of Western Australia , Nedlands, Western Australia , Australia.


Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause with a median survival of only three 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 is fibroblasts, and senescent fibroblasts have been identified in the lungs of patients with IPF 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 signal transducer and activator of transcription 3 (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 summarizes what is presently known about fibroblast senescence in IPF and how STAT3 may contribute to this phenotype.


fibroblast senescence; idiopathic pulmonary fibrosis; signal transducer and activator of transcription 3

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