Intermedin protects against sepsis by concurrently re-establishing the endothelial barrier and alleviating inflammatory responses

被引：49

作者：

Xiao, Fei ^{[1
,2
]}

Wang, Denian ^{[1
]}

Kong, Lingmiao ^{[1
]}

Li, Min ^{[1
]}

Feng, Zhongxue ^{[1
]}

Shuai, Bingxing ^{[3
]}

Wang, Lijun ^{[1
]}

Wei, Yong'gang ^{[4
]}

Li, Hongyu ^{[4
]}

Wu, Sisi ^{[1
]}

Tan, Chun ^{[1
]}

Zhao, Huan ^{[1
]}

Hu, Xuejiao ^{[5
]}

Liu, Jin ^{[6
]}

Kang, Yan ^{[3
]}

Liao, Xuelian ^{[3
]}

Zhou, Yan ^{[3
]}

Zhang, Wei ^{[1
]}

机构：

[1] Sichuan Univ, West China Hosp, Collaborat Innovat Ctr Biotherapy, Mol Med Res Ctr,State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China

[2] Sichuan Univ, West China Univ Hosp 2, Dept Intens Care, Unit Gynecol & Obstet, Chengdu 610041, Sichuan, Peoples R China

[3] Sichuan Univ, West China Hosp, Dept Intens Care Unit, Chengdu 610041, Sichuan, Peoples R China

[4] Sichuan Univ, West China Hosp, Dept Liver Surg, Chengdu 610041, Sichuan, Peoples R China

[5] Sichuan Univ, West China Hosp, Dept Lab Med, Chengdu 610041, Sichuan, Peoples R China

[6] Sichuan Univ, West China Hosp, Dept Anesthesiol, Chengdu 610041, Sichuan, Peoples R China

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

CHEMOKINE RECEPTOR 2; SEPTIC SHOCK; VASCULAR-PERMEABILITY; CELL PERMEABILITY; GROWTH-FACTOR; BONE-MARROW; VE-CADHERIN; DEFINITIONS; STABILIZES; MONOCYTES;

D O I：

10.1038/s41467-018-05062-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Sepsis is a life-threatening condition caused by dysregulated host responses to infection. Widespread vascular hyperpermeability and a "cytokine storm" are two pathophysiological hallmarks of sepsis. Here, we show that intermedin (IMD), a member of the calcitonin family, alleviates organ injury and decreases mortality in septic mice by concurrently alleviating vascular leakage and inflammatory responses. IMD promotes the relocation of vascular endothelial cadherin through a Rab11-dependent pathway to dynamically repair the disrupted endothelial junction. Additionally, IMD decreases inflammatory responses by reducing macrophage infiltration via downregulating CCR2 expression. IMD peptide administration ameliorates organ injuries and significantly improves the survival of septic mice, and the experimental results correlate with the clinical data. Patients with high IMD levels exhibit a lower risk of shock, lower severity scores, and greatly improved survival outcomes than those with low IMD levels. Based on our data, IMD may be an important self-protective factor in response to sepsis.

引用

页数：15

共 49 条

[1] The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome [J].