Radiation Induced Pulmonary Fibrosis As a Model of Progressive Fibrosis: Contributions of DNA Damage, Inflammatory Response and Cellular Senescence Genes

Overview

Journal Exp Lung Res

Publisher Informa Healthcare

Specialty Pulmonary Medicine

Date 2017 May 24

PMID 28534660

Citations 26

Authors

Tyler A Beach

Carl J Johnston

Angela M Groves

Jacqueline P Williams

Jacob N Finkelstein

Affiliations

Soon will be listed here.

Abstract

Materials And Methods: In an established model of RIPF, C57BL/6J mice were exposed to 12.5 Gy thorax irradiation and sacrificed at 24 hours, 1, 4, 12, and 32 weeks following exposure, and lung tissue was compared to age-matched controls by RNA sequencing.

Results: Of 176 PF associated gene transcripts identified by database interrogation, 146 (>82%) were present in our experimental model, throughout the progression of RIPF. Analysis revealed that nearly 85% of PF gene transcripts were associated with at least 1 other search term. Furthermore, of 22 genes common to all four terms, 16 were present experimentally in RIPF.

Conclusions: This illustrates the validity of RIPF as a model of progressive PF/IPF based on the numbers of transcripts reported in both literature and observed experimentally. Well characterized genes and proteins are implicated in this model, supporting the hypotheses that DNA damage, inflammatory response and cellular senescence are associated with the pathogenesis of PF.

Citing Articles

Thrombopoietin mimetic reduces mouse lung inflammation and fibrosis after radiation by attenuating activated endothelial phenotypes.

English J, Dhanikonda S, Tanaka K, Koba W, Eichenbaum G, Yang W JCI Insight. 2024; 9(21).

PMID: 39513364 PMC: 11601560. DOI: 10.1172/jci.insight.181330.

Mitochondria Energy Metabolism Depression as Novel Adjuvant to Sensitize Radiotherapy and Inhibit Radiation Induced-Pulmonary Fibrosis.

Zhou Z, Jiang X, Yi L, Li C, Wang H, Xiong W Adv Sci (Weinh). 2024; 11(26):e2401394.

PMID: 38715382 PMC: 11234447. DOI: 10.1002/advs.202401394.

Transcriptional Changes in Radiation-Induced Lung Injury: A Comparative Analysis of Two Radiation Doses for Preclinical Research.

Farh M, Kim H, Kim S, Lee J, Lee H, Cui R Int J Mol Sci. 2024; 25(7).

PMID: 38612576 PMC: 11011446. DOI: 10.3390/ijms25073766.

Epithelial Responses in Radiation-Induced Lung Injury (RILI) Allow Chronic Inflammation and Fibrogenesis.

Beach T, Finkelstein J, Chang P Radiat Res. 2023; 199(5):439-451.

PMID: 37237442 PMC: 10498477. DOI: 10.1667/RADE-22-00103.1.

Mitochondrial Signaling Pathways Associated with DNA Damage Responses.

Shimura T Int J Mol Sci. 2023; 24(7).

PMID: 37047099 PMC: 10094106. DOI: 10.3390/ijms24076128.

References

Minagawa S, Araya J, Numata T, Nojiri S, Hara H, Yumino Y . Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-β-induced senescence of human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2011; 300(3):L391-401. PMC: 3284316. DOI: 10.1152/ajplung.00097.2010. View

You H, Wei L, Sun W, Wang L, Yang Z, Liu Y . The green tea extract epigallocatechin-3-gallate inhibits irradiation-induced pulmonary fibrosis in adult rats. Int J Mol Med. 2014; 34(1):92-102. PMC: 4072398. DOI: 10.3892/ijmm.2014.1745. View

Raghu G, Brown K, Costabel U, Cottin V, du Bois R, Lasky J . Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. Am J Respir Crit Care Med. 2008; 178(9):948-55. DOI: 10.1164/rccm.200709-1446OC. View

Hardie W, Hagood J, Dave V, Perl A, Whitsett J, Korfhagen T . Signaling pathways in the epithelial origins of pulmonary fibrosis. Cell Cycle. 2010; 9(14):2769-76. PMC: 3040960. DOI: 10.4161/cc.9.14.12268. View

Pala L, Giannini S, Rosi E, Cresci B, Scano G, Mohan S . Direct measurement of IGF-I and IGFBP-3 in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis. J Endocrinol Invest. 2002; 24(11):856-64. DOI: 10.1007/BF03343942. View

Soumyakrishnan S, Divya T, Kalayarasan S, Sriram N, Sudhandiran G . Daidzein exhibits anti-fibrotic effect by reducing the expressions of Proteinase activated receptor 2 and TGFβ1/smad mediated inflammation and apoptosis in Bleomycin-induced experimental pulmonary fibrosis. Biochimie. 2014; 103:23-36. DOI: 10.1016/j.biochi.2014.04.005. View

Borensztajn K, Crestani B, Kolb M . Idiopathic pulmonary fibrosis: from epithelial injury to biomarkers--insights from the bench side. Respiration. 2013; 86(6):441-52. DOI: 10.1159/000357598. View

Kalash R, Berhane H, Goff J, Houghton F, Epperly M, Dixon T . Effects of thoracic irradiation on pulmonary endothelial compared to alveolar type-II cells in fibrosis-prone C57BL/6NTac mice. In Vivo. 2013; 27(3):291-7. PMC: 3783952. View

Povedano J, Martinez P, Flores J, Mulero F, Blasco M . Mice with Pulmonary Fibrosis Driven by Telomere Dysfunction. Cell Rep. 2015; 12(2):286-99. DOI: 10.1016/j.celrep.2015.06.028. View

10.

Wollin L, Maillet I, Quesniaux V, Holweg A, Ryffel B . Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther. 2014; 349(2):209-20. DOI: 10.1124/jpet.113.208223. View

11.

Dai J, Cai H, Zhuang Y, Wu Y, Min H, Li J . Telomerase gene mutations and telomere length shortening in patients with idiopathic pulmonary fibrosis in a Chinese population. Respirology. 2014; 20(1):122-8. DOI: 10.1111/resp.12422. View

12.

Graves P, Siddiqui F, Anscher M, Movsas B . Radiation pulmonary toxicity: from mechanisms to management. Semin Radiat Oncol. 2010; 20(3):201-7. DOI: 10.1016/j.semradonc.2010.01.010. View

13.

Chilosi M, Carloni A, Rossi A, Poletti V . Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema. Transl Res. 2013; 162(3):156-73. DOI: 10.1016/j.trsl.2013.06.004. View

14.

Rodier F, Campisi J . Four faces of cellular senescence. J Cell Biol. 2011; 192(4):547-56. PMC: 3044123. DOI: 10.1083/jcb.201009094. View

15.

Coppe J, Patil C, Rodier F, Sun Y, Munoz D, Goldstein J . Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008; 6(12):2853-68. PMC: 2592359. DOI: 10.1371/journal.pbio.0060301. View

16.

Phillips R, Burdick M, Hong K, Lutz M, Murray L, Xue Y . Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest. 2004; 114(3):438-46. PMC: 484979. DOI: 10.1172/JCI20997. View

17.

Selman M, King T, Pardo A . Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med. 2001; 134(2):136-51. DOI: 10.7326/0003-4819-134-2-200101160-00015. View

18.

Segel M, Izbicki G, Cohen P, Or R, Christensen T, Wallach-Dayan S . Role of interferon-gamma in the evolution of murine bleomycin lung fibrosis. Am J Physiol Lung Cell Mol Physiol. 2003; 285(6):L1255-62. DOI: 10.1152/ajplung.00303.2002. View

19.

Olman M, Mackman N, Gladson C, Moser K, Loskutoff D . Changes in procoagulant and fibrinolytic gene expression during bleomycin-induced lung injury in the mouse. J Clin Invest. 1995; 96(3):1621-30. PMC: 185788. DOI: 10.1172/JCI118201. View

20.

Wolters P, Collard H, Jones K . Pathogenesis of idiopathic pulmonary fibrosis. Annu Rev Pathol. 2013; 9:157-79. PMC: 4116429. DOI: 10.1146/annurev-pathol-012513-104706. View