PMID- 34517882
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210917
IS  - 1745-6673 (Print)
IS  - 1745-6673 (Electronic)
IS  - 1745-6673 (Linking)
VI  - 16
IP  - 1
DP  - 2021 Sep 13
TI  - Genome-wide mRNA profiling identifies the NRF2-regulated lymphocyte oxidative 
      stress status in patients with silicosis.
PG  - 40
LID - 10.1186/s12995-021-00332-0 [doi]
LID - 40
AB  - BACKGROUND: The immunomodulatory abnormalities of silicosis are related to the 
      lymphocyte oxidative stress state. The potential effect of antioxidant therapy on 
      silicosis may depend on the variation in nuclear factor erythroid 2-related 
      factor 2 (NRF2)-regulated antioxidant genes in peripheral blood mononuclear cells 
      (PBMCs). As NRF2 is a redox-sensitive transcription factor, its possible roles 
      and underlying mechanism in the treatment of silicosis need to be clarified. 
      METHODS: Ninety-two male patients with silicosis and 87 male healthy volunteers 
      were randomly selected. PBMCs were isolated from fresh blood from patients with 
      silicosis and healthy controls. The lymphocyte oxidative stress state was 
      investigated by evaluating NRF2 expression and NRF2-dependent antioxidative genes 
      in PBMCs from patients with silicosis. Key differentially expressed genes (DEGs) 
      and signaling pathways were identified utilizing RNA sequencing (RNA-Seq) and 
      bioinformatics technology. Gene set enrichment analysis was used to identify the 
      differences in NRF2 signaling networks between patients with silicosis and 
      healthy controls. RESULTS: The number of monocytes was significantly higher in 
      patients with silicosis than that of healthy controls. Furthermore, RNA-Seq 
      findings were confirmed using quantitative polymerase chain reaction and revealed 
      that NRF2-regulated DEGs were associated with glutathione metabolism, 
      transforming growth factor-beta, and the extracellular matrix receptor interaction 
      signaling pathway in PBMCs from patients with silicosis. The top 10 hub genes 
      were identified by PPI analysis: SMAD2, MAPK3, THBS1, SMAD3, ITGB3, integrin 
      alpha-V (ITGAV), von Willebrand factor (VWF), BMP4, CD44, and SMAD7. CONCLUSIONS: 
      These findings suggest that NRF2 signaling regulates the lymphocyte oxidative 
      stress state and may contribute to fibrogenic responses in human PBMCs. 
      Therefore, NRF2 might serve as a novel preventive and therapeutic candidate for 
      silicosis.
CI  - (c) 2021. The Author(s).
FAU - Zhao, Yingzheng
AU  - Zhao Y
AD  - School of Public Health, North China University of Science and Technology, 
      Tangshan, Hebei Province, 063009, People's Republic of China.
AD  - School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 
      453003, People's Republic of China.
FAU - Xu, Guangcui
AU  - Xu G
AD  - School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 
      453003, People's Republic of China.
FAU - Li, Haibin
AU  - Li H
AD  - School of Public Health, North China University of Science and Technology, 
      Tangshan, Hebei Province, 063009, People's Republic of China.
AD  - School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 
      453003, People's Republic of China.
FAU - Chang, Meiyu
AU  - Chang M
AD  - School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 
      453003, People's Republic of China.
FAU - Xiong, Cheng
AU  - Xiong C
AD  - School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 
      453003, People's Republic of China.
FAU - Tao, Yingjun
AU  - Tao Y
AD  - School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 
      453003, People's Republic of China.
FAU - Guan, Yi
AU  - Guan Y
AD  - School of Public Health, North China University of Science and Technology, 
      Tangshan, Hebei Province, 063009, People's Republic of China.
FAU - Li, Yuchun
AU  - Li Y
AD  - School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 
      453003, People's Republic of China.
FAU - Yao, Sanqiao
AU  - Yao S
AD  - School of Public Health, North China University of Science and Technology, 
      Tangshan, Hebei Province, 063009, People's Republic of China. sanqiaoyao@qq.com.
AD  - School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province, 
      453003, People's Republic of China. sanqiaoyao@qq.com.
LA  - eng
GR  - 81773399/Innovative Research Group Project of the National Natural Science 
      Foundation of China/
GR  - 81703183/Innovative Research Group Project of the National Natural Science 
      Foundation of China (CN)/
PT  - Journal Article
DEP - 20210913
PL  - England
TA  - J Occup Med Toxicol
JT  - Journal of occupational medicine and toxicology (London, England)
JID - 101245790
PMC - PMC8436508
OTO - NOTNLM
OT  - Fibrosis
OT  - GSEA-analysis
OT  - Nuclear factor-erythroid 2-related factor 2
OT  - Peripheral blood mononuclear cells
OT  - Silicosis
COIS- The authors declare that they have no competing interests.
EDAT- 2021/09/15 06:00
MHDA- 2021/09/15 06:01
PMCR- 2021/09/13
CRDT- 2021/09/14 05:43
PHST- 2021/02/24 00:00 [received]
PHST- 2021/08/30 00:00 [accepted]
PHST- 2021/09/14 05:43 [entrez]
PHST- 2021/09/15 06:00 [pubmed]
PHST- 2021/09/15 06:01 [medline]
PHST- 2021/09/13 00:00 [pmc-release]
AID - 10.1186/s12995-021-00332-0 [pii]
AID - 332 [pii]
AID - 10.1186/s12995-021-00332-0 [doi]
PST - epublish
SO  - J Occup Med Toxicol. 2021 Sep 13;16(1):40. doi: 10.1186/s12995-021-00332-0.