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. 2019 May;120(5):8547-8560.
doi: 10.1002/jcb.28142. Epub 2018 Dec 5.

Mitochondrial DNA plays an important role in lung injury induced by sepsis

Zhenguo Zeng  1 , Dan Li  1 , Fen Liu  1 , Chaoqi Zhou  1 , Qiang Shao  1 , Chengzhi Ding  1 , Cheng Qing  1 , Xuzhen Wang  1 , Zhiguo Hu  2 , Kejian Qian  1
Affiliations

Mitochondrial DNA plays an important role in lung injury induced by sepsis

Zhenguo Zeng et al. J Cell Biochem. 2019 May.

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.

Keywords: TLR9/MyD88/NF-κB; lung injury; mitochondrial DNA; sepsis.

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References

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