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Mitochondrial DNA plays an important role in lung injury induced by sepsis
Author(s) -
Zeng Zhenguo,
Li Dan,
Liu Fen,
Zhou Chaoqi,
Shao Qiang,
Ding Chengzhi,
Qing Cheng,
Wang Xuzhen,
Hu Zhiguo,
Qian Kejian
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28142
Subject(s) - apoptosis , tlr9 , microbiology and biotechnology , tumor necrosis factor alpha , mitochondrial dna , small interfering rna , biology , western blot , downregulation and upregulation , cell , gene , gene expression , immunology , rna , biochemistry , dna methylation
Abstract The effects and mechanisms of mitochondrial DNA (mtDNA) in the development of sepsis‐induced lung injury is not well understood. In our present study, we studied the mtDNA effects in sepsis‐induced lung injury model, in vitro and in vivo. Compared with the Normal group, the lung histopathological score, the number of positive apoptosis cell, wet/dry ( W / D) ratio and TNF‐α, IL‐1β, and IL‐6 concentrations of lipopolysaccharides (LPSs) and mtDNA groups were significantly increased ( P < 0.001, respectively). Meanwhile, the lung histopathological score, positive W / D ratio, number of apoptosis cell and tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, and IL‐6 concentrations of LPS + mtDNA and small interfering RNA (siRNA)‐NC + LPS + mtDNA groups were significantly upregulated compared with those of LPS group ( P < 0.05, respectively). However, the lung histopathological score, the number of positive apoptosis cell, W / D ratio and TNF‐α, IL‐1β, and IL‐6 concentrations were significantly improved within the toll‐like receptor (TLR9)siRNA + LPS + mtDNA group compared with the LPS group ( P < 0.01, respectively). The TLR9, MyD88, and NF‐κB proteins or gene expressions of the LPS group and mtDNA group were significantly upregulated compared with those of Normal group by Western blot analysis or immunohistochemistry assay ( P < 0.01, respectively), and the TLR9, MyD88, and NF‐κB proteins or gene expressions of LPS + mtDNA and siRNA‐NC + LPS + mtDNA groups were significantly enhanced compared with those of LPS group ( P < 0.05, respectively). However, the TLR9, MyD88, and NF‐κB proteins or gene expressions of TLR9siRNA + LPS + mtDNA group were significantly suppressed compared with those of the LPS group ( P < 0.01, respectively). In conclusion, mtDNA could provoke lung injury induced by sepsis via regulation of TLR9/MyD88/NF‐κB pathway in vitro and in vivo.