Netrin-1 Dampens Hypobaric Hypoxia-Induced Lung Injury in Mice

Ching Lung Ko, Jui An Lin, Kung Yen Chen, An Chih Hsu, Shu Yu Wu, Yu Ting Tai, Ko Huan Lin, Wei Chen Chung, Min Hui Li

Research output: Contribution to journalArticlepeer-review

Abstract

Background: This study aimed to explore the effects of netrin-1 on hypobaric hypoxia-induced lung injury in mice. Methods: We exposed 6-8-week-old C57BL/6 mice to hypobaric stress at 340 mmHg for 30 minutes followed by 260 mmHg for different periods (6, 12, 18, and 24 hours) to observe the severity of lung injury (O2 concentration, 21%; 54.6 mmHg). The wet/dry weight ratio and protein leakage from the mouse lung were used to determine the suitable exposure time. Netrin-1 was injected into the tail vein of mice before 18-hour decompression. Inflammatory cytokines, lung injury scores, and activity of nuclear factor κB were evaluated. The expression of apoptosis-related proteins was also examined. Results: Protein concentration in the bronchoalveolar lavage fluid was significantly higher in the 18-hour group (p < 0.05). Pulmonary pathology revealed neutrophil infiltration, alveolar septum thickening, and tissue edema. Injury score and macrophage inflammatory protein 2 levels were also increased. Intrinsic apoptosis pathway was activated. Hypoxia decreased the expression of Bcl2 protein, the number of active caspase-3-stained cells, and UNC5HB receptors. Pretreatment with netrin-1 reduced protein leakage, inhibited neutrophil migration, lowered the injury score, attenuated apoptosis, and increased UNC5HB receptor expression. Conclusion: Netrin-1 dampens hypobaric hypoxia-induced lung injury by inhibiting neutrophil migration and attenuating apoptosis.

Original languageEnglish
Pages (from-to)293-302
Number of pages10
JournalHigh Altitude Medicine and Biology
Volume20
Issue number3
DOIs
Publication statusPublished - Sep 2019

Keywords

  • acute lung injury
  • apoptosis
  • hypobaric hypoxia
  • mice
  • netrin-1

ASJC Scopus subject areas

  • Physiology
  • Public Health, Environmental and Occupational Health

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