A Novel Peroxisome Proliferator-Activated Receptor Gamma/Nuclear Factor-Kappa B Activation Pathway is Involved in the Protective Effect of Adipose-Derived Mesenchymal Stem Cells Against Ischemia-Reperfusion Lung Injury

新型过氧化物酶体增殖激活受体γ/核因子κB激活通路参与脂肪间充质干细胞对缺血再灌注肺损伤的保护作用

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作者:Yudai Miyashita, Takashi Kanou, Eriko Fukui, Takahiro Matsui, Toru Kimura, Naoko Ose, Soichiro Funaki, Yasushi Shintani

Background

Adipose-derived stem cells (ADSCs) are well-recognized for their remarkable ability to suppress ischemia-reperfusion lung injury (IRLI). The primary

Conclusion

Administration of ADSCs exerted a significant protective effect against IRLI in mice, and the effect is attributed to the activation of the PPARγ/NF-κB pathway.

Methods

A warm hilar occlusion model in C57BL6J mice was used. Hilar occlusion was achieved for 1 hour (ischemic), and after 1 hour the occlusion was released (reperfusion) to recover for 3 hours. RNA sequencing, the physiological function, pathway activation, and expression of inflammatory cytokines were evaluated.

Results

Lung gas exchange and pulmonary edema were significantly improved in the IRLI/ADSCs group compared with the IRLI group. RNA sequencing results suggested that the peroxisome proliferator-activated receptor gamma (PPARγ)/nuclear factor-kappa B (NF-κB) pathway was involved in the effect of the ADSCs. Administration of a PPARγ antagonist in the IRLI/ADSC group resulted in the deterioration of the physiological function. Furthermore, the PPARγ protein expression level decreased, the NF-κB protein expression level increased, and inflammatory cytokine parameters from lung tissue and blood sample worsened in the PPARγ antagonist-administered group.

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