Exercise hormone irisin mitigates endothelial barrier dysfunction and microvascular leakage–related diseases
Jianbin Bi, Jia Zhang, Yifan Ren, Zhaoqing Du, Yuanyuan Zhang, Chang Liu, Yawen Wang, Lin Zhang, Zhihong Shi, Zheng Wu, Yi Lv, Rongqian Wu
Jianbin Bi, Jia Zhang, Yifan Ren, Zhaoqing Du, Yuanyuan Zhang, Chang Liu, Yawen Wang, Lin Zhang, Zhihong Shi, Zheng Wu, Yi Lv, Rongqian Wu
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Research Article Cell biology Vascular biology

Exercise hormone irisin mitigates endothelial barrier dysfunction and microvascular leakage–related diseases

Abstract

Increased microvascular leakage is a cardinal feature of many critical diseases. Regular exercise is associated with improved endothelial function and reduced risk of cardiovascular disease. Irisin, secreted during exercise, contributes to many health benefits of exercise. However, the effects of irisin on endothelial function and microvascular leakage remain unknown. In this study, we found that irisin remarkably strengthened endothelial junctions and barrier function via binding to integrin αVβ5 receptor in LPS-treated endothelial cells. The beneficial effect of irisin was associated with suppression of the Src–MLCK–β-catenin pathway, activation of the AMPK-Cdc42/Rac1 pathway, and improvement of mitochondrial function. In preclinical models of microvascular leakage, exogenous irisin improved pulmonary function, decreased lung edema and injury, suppressed inflammation, and increased survival. In ARDS patients, serum irisin levels were decreased and inversely correlated with disease severity and mortality. In conclusion, irisin enhances endothelial barrier function and mitigates microvascular leakage–related diseases.

Authors

Jianbin Bi, Jia Zhang, Yifan Ren, Zhaoqing Du, Yuanyuan Zhang, Chang Liu, Yawen Wang, Lin Zhang, Zhihong Shi, Zheng Wu, Yi Lv, Rongqian Wu

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Exogenous irisin administration alleviated microvascular leakage–related diseases.

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Exogenous irisin administration alleviated microvascular leakage–related...
Irisin was given by i.v. administration (250 μg/kg, a single dose) immediately or 6 hours after LPS administration intratracheally (2 mg/kg), and immediately after CLP operation. Irisin neutralizing antibody was administrated by i.v. injection in mice (50 μg/kg, a single dose) 24 hours before LPS was administrated intratracheally. Vehicle group of mice was given equivalent amounts of saline. At 24 hours after LPS was administrated intratracheally or 21 hours after CLP operation, lung tissue, BALF, and arterial blood samples were collected. (A) Serum irisin levels. (B and C) Total cells and protein levels in BALF in LPS-induced lung microvascular leakage. (D) Water content of lungs. (E) H&E staining in LPS-induced lung microvascular leakage. Scale bar: 50 μm. (F) ALI scores. (G) At 24 hours after LPS administration, arterial blood was obtained from the abdominal aorta, and PaO2 was assessed via blood gas analyzer. (H) PaCO2 levels. (I) H&E staining of lung in CLP-induced sepsis. Scale bar: 50 µm. (J) ALI score. (K) Water content. (L and M) Total cells and protein levels in BALF in CLP-induced sepsis. (N) Seven-day survival study in CLP-induced sepsis. Kaplan-Meier curves were used for survival analysis and log-rank testing for difference analysis. High irisin represents a dose of 250 μg/kg. Low irisin represents a dose of 50 μg/kg; n = 6 per group, mean ± SEM. *P < 0.05 versus the sham group, #P < 0.05 versus the LPS or CLP group. One-way ANOVA was used to analyze the differences between groups.