Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Attenuate LPS-Induced ARDS by Modulating Macrophage Polarization Through Inhibiting Glycolysis in Macrophages

被引：119

作者：

Deng, Huimin ^{[1
]}

Wu, Lingmin ^{[2
]}

Liu, Meiyun ^{[1
]}

Zhu, Lina ^{[1
]}

Chen, Yuanli ^{[1
]}

Zhou, Huanping ^{[1
]}

Shi, Xuan ^{[1
]}

Wei, Juan ^{[1
]}

Zheng, Li ^{[3
]}

Hu, Xiaoting ^{[4
]}

Wang, Mansi ^{[5
]}

He, Zhengyu ^{[4
]}

Lv, Xin ^{[1
]}

Yang, Hao ^{[1
]}

机构：

[1] Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Anesthesiol, 507 Thenginin Rd, Shanghai 200433, Peoples R China

[2] Anhui Med Univ, Hosp 1, Dept Anesthesiol, Hefei, Peoples R China

[3] Anhui Med Univ, Fuyang Hosp, Dept Anesthesiol, Fuyang, Peoples R China

[4] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Crit Care Med, Shanghai, Peoples R China

[5] Fudan Univ, Shanghai Med Coll, Shanghai Canc Ctr, Dept Pathol, Shanghai, Peoples R China

来源：

SHOCK | 2020年 / 54卷 / 06期

基金：

中国国家自然科学基金;

关键词：

ARDS; BMSCs; exosome; glycolysis; HIF-1α inflammation; macrophages;

D O I：

10.1097/SHK.0000000000001549

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Macrophages play a key role in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that glycolysis plays an important role in regulating macrophage polarization through metabolic reprogramming. Bone marrow mesenchymal stem cells (BMSCs) can alleviate sepsis-induced lung injury and possess potent immunomodulatory and immunosuppressive properties via secreting exosomes. However, it is unknown whether BMSCs-derived exosomes exert their therapeutic effect against sepsis-induced lung injury by inhibiting glycolysis in macrophages. Therefore, the present study aimed to evaluate the anti-inflammatory effects of exosomes released from BMSCs on acute lung injury induced by lipopolysaccharide (LPS) in mice and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs inhibited M1 polarization and promoted M2 polarization in MH-S cells (a murine alveolar macrophage cell line) by releasing exosomes. Further experiments showed that exosomes secreted by BMSCs modulated LPS-treated MH-S cells polarization by inhibiting cellular glycolysis. Moreover, our results showed that BMSCs-derived exosomes down-regulated the expression of several essential proteins of glycolysis via inhibition of hypoxia-inducible factor 1 (HIF-1)alpha. Finally, a model of LPS-induced ARDS in mice was established, we found that BMSCs-derived exosomes ameliorated the LPS-induced inflammation and lung pathological damage. Meanwhile, we found that intratracheal delivery of BMSCs-derived exosomes effectively down-regulated LPS-induced glycolysis in mice lung tissue. These findings reveal new mechanisms of BMSCs-derived exosomes in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of LPS-induced ARDS.

引用

页码：828 / 843

页数：16

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