期刊
RESPIRATORY RESEARCH
卷 23, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12931-022-02118-2
关键词
Protein tyrosine phosphatase receptor type O (PTPRO); Hemorrhage shock (HS); Lung injury; Inflammation; The NF-kappa B signaling pathway
资金
- Precision Medicine Project of Wuxi Municipal Healthy Commission [J202007]
- Key Scientific Research Project of Wuxi Municipal Healthy Commission [Z202105]
- Science and Technology Development Fund Project of Wuxi [Y20212057]
- Wuxi Top Medical Expert Team of Taihu Talent Program
This study demonstrated that PTPRO knockdown may contribute to attenuating inflammation in HS-induced lung injury via inhibiting NF-kappa B pathway activation.
Background: Hemorrhage shock (HS) is characterized by decreased tissue oxygenation and organ damage due to severe blood loss. Protein tyrosine phosphatase receptor type O (PTPRO) is abnormally up-regulated in the rat lungs after trauma/HS. Methods: To elucidate the regulatory mechanism of PTPRO in lung inflammation following HS, we established a rat model of HS via withdrawing blood by a catheter inserted into the femoral artery followed by resuscitation. The rats were infected with lentivirus harboring short hairpin RNA (shRNA) targeting PTPRO by intratracheal instillation. Results: PTPRO was significantly up-regulated in rat lungs after HS. PTPRO knockdown enhanced epithelial integrity and reduced capillary leakage by up-regulating tight junction proteins zonula occludens-1 (ZO-1) and occludin (OCC) in the lungs. Besides, HS-induced myeloperoxidase activity and inflammatory cell infiltration was mitigated by PTPRO knockdown. The expression of inflammatory cytokines/chemokines (TNF-alpha, IL-6, MIP-2, MCP-1, and KC) in the lungs and bronchoalveolar lavage fluid was regressed after PTPRO knockdown. The nuclear factor kappa B (NF-kappa B) pathway was involved in HS-induced lung inflammation. PTPRO down-regulation inhibited the NF-kappa B pathway activation by suppressing the phosphorylation of NF-kappa B and its translocation from the cytoplasm into the nucleus in HS. Conclusion: Taken together, we demonstrated that PTPRO knockdown may contribute to attenuating inflammation in HS-induced lung injury via inhibiting NF-kappa B pathway activation.
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