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8-Oxoguanine target...
8-Oxoguanine targeted by 8-oxoguanine DNA glycosylase 1 (OGG1) is central to fibrogenic gene activation upon lung injury
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- Pan, Lang (author)
- University of Texas Medical Branch
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- Hao, Wenjing (author)
- University of Texas Medical Branch
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- Xue, Yaoyao (author)
- University of Texas Medical Branch
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- Wang, Ke (author)
- University of Texas Medical Branch
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- Zheng, Xu (author)
- University of Texas Medical Branch
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- Luo, Jixian (author)
- University of Texas Medical Branch,Shanxi University
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- Ba, Xueqing (author)
- University of Texas Medical Branch,Northeast Normal University
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Xiang, Yang (author)
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Qin, Xiaoqun (author)
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- Bergwik, Jesper (author)
- Lund University,Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Tanner, Lloyd (author)
- Lund University,Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Nya strategier för att förhindra skadlig luftvägsinflammation,Forskargrupper vid Lunds universitet,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Novel strategies targeting detrimental airway inflammation,Lund University Research Groups,Skåne University Hospital
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- Egesten, Arne (author)
- Lund University,Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Nya strategier för att förhindra skadlig luftvägsinflammation,Forskargrupper vid Lunds universitet,Hereditärt angioödem (HAE) – epidemiologi, genetik och patofysiologi,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Novel strategies targeting detrimental airway inflammation,Lund University Research Groups,Hereditary angioedema (HAE) – epidemiology, genetics and pathophysiology,Skåne University Hospital
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- Brasier, Allan R. (author)
- University of Wisconsin-Madison
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- Boldogh, Istvan (author)
- University of Texas Medical Branch
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(creator_code:org_t)
- 2023-01-18
- 2023
- English 16 s.
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 51:3, s. 1087-1102
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Abstract
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- Reactive oxygen species (ROS) are implicated in epithelial cell-state transition and deposition of extracellular matrix upon airway injury. Of the many cellular targets of ROS, oxidative DNA modification is a major driving signal. However, the role of oxidative DNA damage in modulation profibrotic processes has not been fully delineated. Herein, we report that oxidative DNA base lesions, 8-oxoG, complexed with 8-oxoguanine DNA glycosylase 1 (OGG1) functions as a pioneer factor, contributing to transcriptional reprogramming within airway epithelial cells. We show that TGFβ1-induced ROS increased 8-oxoG levels in open chromatin, dynamically reconfigure the chromatin state. OGG1 complexed with 8-oxoG recruits transcription factors, including phosphorylated SMAD3, to pro-fibrotic gene promoters thereby facilitating gene activation. Moreover, 8-oxoG levels are elevated in lungs of mice subjected to TGFβ1-induced injury. Pharmacologic targeting of OGG1 with the selective small molecule inhibitor of 8-oxoG binding, TH5487, abrogates fibrotic gene expression and remodeling in this model. Collectively, our study implicates that 8-oxoG substrate-specific binding by OGG1 is a central modulator of transcriptional regulation in response to tissue repair.
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Medicinsk bioteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Medical Biotechnology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Pan, Lang
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Hao, Wenjing
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Xue, Yaoyao
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Wang, Ke
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Zheng, Xu
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Luo, Jixian
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show more...
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Ba, Xueqing
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Xiang, Yang
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Qin, Xiaoqun
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Bergwik, Jesper
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Tanner, Lloyd
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Egesten, Arne
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Brasier, Allan R ...
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Boldogh, Istvan
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show less...
- About the subject
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Industrial Biote ...
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and Medical Biotechn ...
- Articles in the publication
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Nucleic Acids Re ...
- By the university
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Lund University