Knockdown of LSD1 meliorates Ox-LDL-stimulated NLRP3 activation and inflammation by promoting autophagy via SESN2-mesiated PI3K/Akt/mTOR signaling pathway
- Life Sci. 2019 Sep 15;233:116696. doi: 10.1016/j.lfs.2019.116696.
- 1. Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, China.
- 2. Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, China. Electronic address: [email protected].
Aims: To explore the mechanism of how LSD1 regulates Autophagy and the correlation between LSD1 and Ox-LDL-induced inflammation.
Main methods: RAW264.7 cells were used during the whole study. Firstly, the effect of Ox-LDL-stimulation on LSD1 expression was detected. Through loss-of-function assay, the associations between LSD1 interference and SESN2 expression, Autophagy, NLRP3 inflammasome and inflammatory cytokines were explored. Finally, the function of LSD1 exerted on activation of PI3K/Akt/mTOR signal pathway was detected using western blotting assay.
Key findings: The expression of LSD1 was significantly elevated in Ox-LDL-treated RAW264.7 cells. Inhibition of LSD1 promoted Autophagy, inhibited inflammation and activated NLRP3 inflammasome. SESN2 was elevated by LSD1 inhibition, and thus activate the PI3K/Akt/mTOR signal pathway. What' more, Knockdown of SESN2 or deactivate the PI3K/Akt/mTOR signal pathway partly reversed the effect of LSD1 inhibition on Autophagy.
Significance: Our present study drew the finding that the knockdown of LSD1 meliorated Ox-LDL-stimulated NLRP3 activation and inflammation through promoting Autophagy via SESN2-mediated PI3K/Akt/mTOR pathway.