PCTR1 improves pulmonary edema fluid clearance through activating the sodium channel and lymphatic drainage in lipopolysaccharide-induced ARDS.

Abstract

Acute respiratory distress syndrome (ARDS) is a lethal clinical syndrome characterized by damage of the epithelial barriers and accumulation of pulmonary edema fluid. Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenously produced lipid mediator, are believed to exert anti-inflammatory and pro-resolution effects. PCTR1 (1 µg/kg) was injected at 8 hr after lipopolysaccharide (LPS; 14 mg/kg) administration, and the rate of pulmonary fluid clearance was measured in live rats at 1 hr after PCTR1 treatment. The primary type II alveolar epithelial cells were cultured with PCTR1 (10 nmol/ml) and LPS (1 μg/ml) for 8 hr. PCTR1 effectively improved pulmonary fluid clearance and ameliorated morphological damage and reduced inflammation of lung tissue, as well as improved the survival rate in the LPS-induced acute lung injury (ALI) model. Moreover, PCTR1 markedly increased sodium channel expression as well as Na, K-ATPase expression and activity in vivo and in vitro. In addition, PCTR1i also upregulated the expression of LYVE-1 in vivo. Besides that, BOC-2, HK7, and LY294002 blocked the promoted effect of PCTR1 on pulmonary fluid clearance. Taken together, PCTR1 upregulates sodium channels' expression via activating the ALX/cAMP/P-Akt/Nedd4-2 pathway and increases Na, K-ATPase expression and activity to promote alveolar fluid clearance. Moreover, PCTR1 also promotes the expression of LYVE-1 to recover the lymphatic drainage resulting in the increase of lung interstitial fluid clearance. In summary, these results highlight a novel systematic mechanism for PCTR1 in pulmonary edema fluid clearance after ALI/ARDS, suggesting its potential role in a therapeutic approach for ALI/ARDS.

• Authors: Pu-Hong Zhang, Jun Han, Fei Cao, Yong-Jian Liu, Chao Tian, Cheng-Hua Wu, Fang Gao Smith, Yu Hao, Sheng-Wei Jin
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 235 Issue 12 Pg. 9510-9523 (12 2020) ISSN: 1097-4652 [Electronic] United States
• PMID: 32529661 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley Periodicals LLC.

Chemical References

• Anti-Inflammatory Agents
• CD59 Antigens
• Cyclin-Dependent Kinase Inhibitor p16
• Epithelial Sodium Channels
• Lipopolysaccharides
• CD59 protein, human
• Docosahexaenoic Acids
• Sodium-Potassium-Exchanging ATPase

Topics

• Acute Lung Injury (chemically induced, drug therapy, pathology)
• Alveolar Epithelial Cells (drug effects, pathology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Body Fluids (drug effects)
• CD59 Antigens (chemistry, genetics, pharmacology)
• Cyclin-Dependent Kinase Inhibitor p16
• Disease Models, Animal
• Docosahexaenoic Acids (chemistry, pharmacology)
• Epithelial Sodium Channels (genetics)
• Gene Expression Regulation (drug effects)
• Humans
• Lipopolysaccharides (toxicity)
• Lung (drug effects, pathology)
• Phosphatidylinositol 3-Kinases (genetics)
• Pulmonary Alveoli (drug effects, pathology)
• Pulmonary Edema (chemically induced, drug therapy, pathology)
• Rats
• Respiratory Distress Syndrome (chemically induced, drug therapy, genetics)
• Signal Transduction (drug effects)
• Sodium-Potassium-Exchanging ATPase (genetics)