Background: Acute lung injury (ALI) induced by sepsis is a common cause of death in clinical practice, and there remains a lack of clinical effective treatment. Cecal ligation and puncture (CLP) is a classic animal model of sepsis, which can induce ALI. Studies have shown that in the lung injury cell model, OGDH (oxoglutarate dehydrogenase) transcription is up-regulated, which is a potential therapeutic target for acute pneumonia. The purpose of this study was to confirm the effects of OGDH on lung injury and inflammation in animal and cell models, and to explore its mechanism.
Methods: By analyzing the GSE16650 gene set, the upregulated OGDH gene was detected in the lung injury cell model. In a sepsis animal model established by CLP and a lung injury cell model, RT-PCR, immunohistochemistry, WB, and other techniques were used to verify the upregulation of OGDH expression, which was then was down-regulated with shRNA to confirm its relationship with ALI. Further, ELISA, RT-PCR, and WB were used to detect the effect of OGDH on the expression of pro-inflammatory factors including IL-1β, IL-6, IL-18, and TNF-α. The downstream pathway of OGDH was predicted using KEGG and GSEA tools and verified by WB and immunofluorescence.
Results: The results showed OGDH was highly expressed in a lung injury cell model and the lung tissue of ALI mice induced by CLP, and downregulation of OGDH alleviated sepsis induced ALI. In animal models and cell models, the expression of OGDH was positively correlated with the expression of pro-inflammatory factors. OGDH may act through the MAPK pathway.
Conclusions: Under the pathological condition of sepsis, OGDH amplifies the inflammatory response through the MAPK pathway, releases pro-inflammatory factors, and induces ALI.
Keywords: MAPK pathway; Oxoglutarate dehydrogenase; acute lung injury (ALI); cecal ligation and puncture (CLP); pro-inflammatory factors.
2021 Journal of Thoracic Disease. All rights reserved.