MUTYH Deficiency Is Associated with Attenuated Pulmonary Fibrosis in a Bleomycin-Induced Model
Joint Authors
Xu, Lizhi
Chen, Jingwen
Ren, Yan
Wu, Xin
Sun, Qingmin
Kang, Jiaqi
Nakabeppu, Yusaku
Wang, Yaping
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-10-23
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible lung disease of unknown etiology with limited survival.
IPF incidence and prevalence increase significantly with aging, which is associated with an age-related accumulation of oxidative DNA damage.
The Mutyh gene is involved in the base excision repair (BER) system, which is critical for repairing the misincorporated adenine that is opposite to the oxidized guanine base, 8-oxoguanine, and maintaining the fidelity of DNA replication.
We used Mutyh knockout mice and a bleomycin-induced pulmonary fibrosis model to test the effect of MUTYH deficiency on lesion progression.
Unexpectedly, a much less severe lesion of pulmonary fibrosis was observed in Mutyh-/- than in Mutyh+/+mice, which was supported by assay on protein levels of TGF-β1 and both fibrotic markers, α-SMA and Vimentin, in pulmonary tissues of the model animals.
Mechanically, MUTYH deficiency prevented the genomic DNA of pulmonary tissue cells from the buildup of single-strand breaks (SSBs) of DNA and maintained the integrity of mtDNA.
Furthermore, increased mitochondrial dynamic regulation and mitophagy were detected in pulmonary tissues of the bleomycin-induced Mutyh-/- model mice, which could reduce the pulmonary epithelial cell apoptosis.
Our results suggested that MUTYH deficiency could even induce protective responses of pulmonary tissue under severe oxidative stress.
American Psychological Association (APA)
Sun, Qingmin& Chen, Jingwen& Xu, Lizhi& Kang, Jiaqi& Wu, Xin& Ren, Yan…[et al.]. 2020. MUTYH Deficiency Is Associated with Attenuated Pulmonary Fibrosis in a Bleomycin-Induced Model. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1204623
Modern Language Association (MLA)
Sun, Qingmin…[et al.]. MUTYH Deficiency Is Associated with Attenuated Pulmonary Fibrosis in a Bleomycin-Induced Model. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1204623
American Medical Association (AMA)
Sun, Qingmin& Chen, Jingwen& Xu, Lizhi& Kang, Jiaqi& Wu, Xin& Ren, Yan…[et al.]. MUTYH Deficiency Is Associated with Attenuated Pulmonary Fibrosis in a Bleomycin-Induced Model. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1204623
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204623