Remote ischemic preconditioning STAT3-dependently ameliorates pulmonary ischemia/reperfusion injury

Nanfu Luo; Jin Liu; Yan Chen; Huan Li; Zhaoyang Hu; Geoffrey W Abbott

doi:10.1371/journal.pone.0196186

Remote ischemic preconditioning STAT3-dependently ameliorates pulmonary ischemia/reperfusion injury

PLoS One. 2018 May 16;13(5):e0196186. doi: 10.1371/journal.pone.0196186. eCollection 2018.

Authors

Nanfu Luo¹, Jin Liu¹, Yan Chen¹, Huan Li¹, Zhaoyang Hu¹, Geoffrey W Abbott²

Affiliations

¹ Laboratory of Anesthesiology & Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
² Bioelectricity Laboratory, Dept. of Physiology and Biophysics, School of Medicine, University of California, Irvine, California, United States of America.

Abstract

The lungs are highly susceptible to injury, including ischemia/reperfusion (I/R) injury. Pulmonary I/R injury can occur when correcting conditions such as primary pulmonary hypertension, and is also relatively common after lung transplantation or other cardiothoracic surgery. Methods to reduce pulmonary I/R injury are urgently needed to improve outcomes following procedures such as lung transplantation. Remote liver ischemic preconditioning (RLIPC) is an effective cardioprotective measure, reducing damage caused by subsequent cardiac I/R injury, but little is known about its potential role in pulmonary protection. Here, we analyzed the efficacy and mechanistic basis of RLIPC in a rat model of pulmonary I/R injury. RLIPC reduced lung I/R injury, lessening structural damage, inflammatory cytokine production and apoptosis. In addition, RLIPC preserved pulmonary function compared to controls following lung I/R injury. RLIPC stimulated phosphorylation of pulmonary STAT3, a component of the SAFE signaling pathway, but not phosphorylation of RISK pathway signaling proteins. Accordingly, STAT3 inhibition using AG490 eliminated the pulmonary protection afforded by RLIPC. Our data demonstrate for the first time that RLIPC protects against pulmonary I/R injury, via a signaling pathway requiring STAT3 phosphorylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Ischemic Preconditioning / methods*
Liver / blood supply*
Lung / blood supply*
Lung Injury / metabolism
Lung Injury / pathology
Lung Injury / prevention & control*
Male
Phosphorylation
Rats
Rats, Sprague-Dawley
Reperfusion Injury / prevention & control*
STAT3 Transcription Factor / metabolism*
Signal Transduction

Substances

STAT3 Transcription Factor
Stat3 protein, rat

Grants and funding

This study was supported by grant No. 81670300 (to ZH) from the National Natural Science Foundation of China, and University of California, Irvine School of Medicine Setup Funds (to GWA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.