Aim
This paper aimed to explore the role and mechanism of SESN2 in septic intestinal dysfunction.
Conclusion
Reduced SESN2 contributed to inflammatory response and barrier dysfunction in septic intestinal dysfunction by promoting ferroptosis via activating the AMPK/Nrf2 signaling pathway.
Methods
Blood samples were collected from patients with septic intestinal dysfunction, and Caco-2 cells were subjected to lipopolysaccharide (LPS) to construct in vitro models. The expression level of SESN2 was determined in the blood samples and cells. The impacts of SESN2 overexpression on cell inflammation, oxidative stress, barrier integrity, and MAPK/Nrf2 signaling were evaluated. To determine the mediated role of MAPK signaling and ferroptosis, AMPK inhibitor (Compound C) and ferroptosis inducer (erastin) were separately used to treat cells, and the influences on the above aspects in cells were assessed.
Objective
Alterations in intestinal function play a crucial role in the pathogenesis of sepsis, and the repair of the intestinal barrier is a potential strategy for the treatment of sepsis. Sestrin2 (SESN2), a highly conserved stress-responsive protein, can be induced in response to stress. Aim: This paper aimed to explore the role and mechanism of SESN2 in septic intestinal dysfunction.
Results
The expression level of SESN2 was down-regulated in patients with septic intestinal dysfunction and LPS-induced cells. SESN2 overexpression was found to suppress cell inflammation and oxidative stress, maintain barrier integrity, and activate AMPK/Nrf2 signaling. Following the AMPK signaling was inhibited or the ferroptosis was triggered, the effects of SESN2 overexpression on the cells were both reversed.