Molecular markers of telomere dysfunction and senescence are common findings in the usual interstitial pneumonia pattern of lung fibrosis. Issue 1 (14th April 2021)

• Record Type: Journal Article
• Authors: Lee, Joyce S; La, Janet; Aziz, Sara; Dobrinskikh, Evgenia; Brownell, Robert; Jones, Kirk D; Achtar‐Zadeh, Natalia; Green, Gary; Elicker, Brett M; Golden, Jeffrey A; Matthay, Michael A; Kukreja, Jasleen; Schwartz, David A; Wolters, Paul J
• Is Part Of: Histopathology. Volume 79:Issue 1(2021)
• Page Start: 67
• Page End: 76
• Publication Date: 2021-04-14
• Subjects: alveolar type II cell -- hypersensitivity pneumonitis -- interstitial lung disease -- pulmonary fibrosis -- rheumatoid arthritis -- scleroderma -- senescence -- telomere; Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.14334
• Languages: English
• ISSNs: 0309-0167

Abstract

Abstract : Aims: Idiopathic pulmonary fibrosis (IPF) is a genetically mediated, age‐associated, progressive form of pulmonary fibrosis characterised pathologically by a usual interstitial pneumonia (UIP) pattern of fibrosis. The UIP pattern is also found in pulmonary fibrosis attributable to clinical diagnoses other than IPF (non‐IPF UIP), whose clinical course is similarly poor, suggesting common molecular drivers. This study investigates whether IPF and non‐IPF UIP lungs similarly express markers of telomere dysfunction and senescence. Methods and results: To test whether patients with IPF and non‐IPF UIP share molecular drivers, lung tissues from 169 IPF patients and 57 non‐IPF UIP patients were histopathologically and molecularly compared. Histopathological changes in both IPF and non‐IPF UIP patients included temporal heterogeneity, microscopic honeycombing, fibroblast foci, and dense collagen fibrosis. Non‐IPF UIP lungs were more likely to have lymphocytic infiltration, non‐caseating granulomas, airway‐centred inflammation, or small airways disease. Telomeres were shorter in alveolar type II (AECII) cells of both IPF and non‐IPF UIP lungs than in those of age‐similar, unused donor, controls. Levels of molecular markers of senescence (p16 and p21) were elevated in lysates of IPF and non‐IPF UIP lungs. Immunostaining localised expression of these proteins to AECII cells. The mucin 5B (MUC5B) gene promoter variant minor allele frequency was similar between IPF and non‐IPF UIP patients, and MUC5B expression was similar in IPF and non‐IPF UIP lungs. Conclusions: Molecular markers of telomere dysfunction and senescence are pathologically expressed in both IPF and non‐IPF UIP lungs. These findings suggest that common molecular drivers may contribute to the pathogenesis of UIP‐associated pulmonary fibrosis, regardless of the clinical diagnosis. Abstract :