Abstract | OBJECTIVES: To investigate the effect of mitochondrial damage-associated molecular patterns on the lung fluid homeostasis in experimental acute lung injury. DESIGN: Experimental study. SETTING: Research laboratory. SUBJECTS: INTERVENTIONS: Samples of bronchoalveolar lavage fluid and serum were obtained from patients and control subjects. Mice were intratracheally instilled with lipopolysaccharide and mitochondrial damage-associated molecular patterns. The primary rat alveolar epithelial type II cells were isolated and incubated with mitochondrial damage-associated molecular patterns. MEASUREMENTS AND MAIN RESULTS: Patients were divided into direct (pulmonary) and indirect (extrapulmonary) injury groups based on etiology. The release of mitochondrial peptide nicotinamide adenine dinucleotide dehydrogenase 1 in both bronchoalveolar lavage fluid and serum was induced in patients and was associated with etiology. In the lipopolysaccharide-induced lung injury, administration of mitochondrial damage-associated molecular patterns exacerbated the lung fluid imbalance, which was mitigated in formyl peptide receptor-1 knockout mice. Proteomic analysis of mouse lung tissues revealed the involvement of ion channels and tight junction proteins in this process. Treatment with mitochondrial damage-associated molecular patterns decreased the expression of epithelial sodium channel α, zonula occludens-1, and occludin via the formyl peptide receptor-1/p38 pathway in the primary rat alveolar epithelial type II cells. CONCLUSIONS: Mitochondrial damage-associated molecular patterns exacerbate lung fluid imbalance in the experimental acute lung injury model through formyl peptide receptor-1 signaling, the inhibition of which may prevent exacerbation of lung fluid imbalance induced by mitochondrial damage-associated molecular patterns. Thus, formyl peptide receptor-1 is a potential therapeutic target for acute respiratory distress syndrome.
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Authors | Zhi-Cheng Yuan, Ni Zeng, Lian Liu, Tao Wang, Lu-Qi Dai, Hao Wang, Zi-Jian Zeng, Yu-Fang Cao, Yong-Fang Zhou, Dan Xu, Yong-Chun Shen, Fu-Qiang Wen |
Journal | Critical care medicine
(Crit Care Med)
Vol. 49
Issue 1
Pg. e53-e62
(01 01 2021)
ISSN: 1530-0293 [Electronic] United States |
PMID | 33165026
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. |
Chemical References |
- FPR1 protein, human
- Receptors, Formyl Peptide
- Electron Transport Complex I
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Topics |
- Acute Lung Injury
(metabolism, pathology)
- Animals
- Bronchoalveolar Lavage Fluid
(chemistry)
- Electron Transport Complex I
(metabolism)
- Humans
- Lung
(metabolism, pathology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mitochondria
(metabolism)
- Rats
- Receptors, Formyl Peptide
(metabolism)
- Respiratory Distress Syndrome
(metabolism)
- Respiratory Mucosa
(metabolism)
- Signal Transduction
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