2. Academic Validation
  3. OGG1 promoted lung fibrosis by activating fibroblasts via interacting with Snail1

OGG1 promoted lung fibrosis by activating fibroblasts via interacting with Snail1

  • Int Immunopharmacol. 2023 Nov 15:126:111148. doi: 10.1016/j.intimp.2023.111148.
Chuge Song 1,  Zhiliang Xu 2,  Qingyun Liang 3,  Yifan Mu 4,  Manqi Liu 5,  Zijun Wu 6,  Xiaomin Li 5,  Jiali Li 6,  Hongqiao Chen 5,  Yahong Wang 7,  Shenglan Gao 7,  Ao Li 7,  Weimin Yao 8,  Gang Liu 9
Affiliations

Affiliations

  • 1 Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China; Department of Respiratory Medicine, Second Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
  • 2 Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China; Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China; Dongguan Institute of Respiratory Medicine, Guangdong Medical University, Dongguan 523121, China. Electronic address: xuzhiliang@gdmu.edu.cn.
  • 3 Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China; Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
  • 4 Department of Respiratory Medicine, Second Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
  • 5 Department of Cardiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
  • 6 Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
  • 7 Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
  • 8 Department of Respiratory Medicine, Second Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China. Electronic address: 490296443@qq.com.
  • 9 Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China; Department of Respiratory and Critical Care Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China. Electronic address: gangliu11@fmmu.edu.cn.
PMID: 37977070 DOI: 10.1016/j.intimp.2023.111148
Abstract

One of abundant DNA lesions induced by Reactive Oxygen Species is 8-oxoguanine (8-oxoG), which compromises genetic instability. 8-oxoG is recognized by the DNA repair protein 8-oxoguanine DNA glycosylase-1 (OGG1) that not only participates in base excision repair but also involves in transcriptional regulation.OGG1 has an important role inIdiopathic Pulmonary Fibrosis (IPF) processing and targeting fibroblasts is a major strategy for the treatment of pulmonary fibrosis, but whether OGG1 activate fibroblast is not clear. In this study, we show that OGG1 expression level is increased at the fibroblast activation stage in mouse lungs induced by bleomycin (BLM) treatment. OGG1 promoted the expression level of fibroblast activation markers (CTGF, fibronectin, and collagen 1) in a pro-fibrotic gene transcriptional regulation pathway via interacting with Snail1, which dependent on 8-oxoG recognition. Global inhibition of OGG1 at the middle stage of lung fibrosis also relieved BLM-induced lung fibrosis in mice. Our results suggest that OGG1 is a target for inhibiting fibroblast activation and a potential therapeutic target for IPF.

Keywords

Fibroblast; IPF; OGG1; Therapeutic target.

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