LncRNA TUG1 has not yet been reported in cerebral ischemia/reperfusion (I/R) injury. Methylcytosine dioxygenase TET2 is involved in ischemic damage. This study aimed to investigate the effects of TUG1 demethylated by TET2 on I/R-induced inflammatory response and identified its possible mechanisms.We found that TUG1 expression was significantly upregulated in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced SH-SY5Y and SK-N-SH cells. Using the middle cerebral artery occlusion (MCAO) mice, we observed a similar effect. We also found that I/R injury could downregulate miR-200a-3p and upregulate NLRP3 and TET2. The knockdown of TUG1 could alleviate OGD/R-induced inflammatory response through upregulating miR-200a-3p and downregulating NLRP3 and other pro-inflammatory molecules. miR-200a-3p inhibition can partially reverse the effects of TUG1 silencing. Further experiments confirmed that TUG1 sponged miR-200a-3p to diminish miR-200a-3p and promote NLRP3 dependent inflammatory responses. Mechanically, knockdown of TET2 induced low levels of TUG1 and high levels of miR-200a-3p in both SK-N-SH and SH-SY5Y cells. IL-18, IL-1β, NLRP3, Caspase-1, and GSDMD-N were highly downregulated in OGD/R-induced SK-N-SH and SH-SY5Y cells after TET2 knockdown. TUG1 overexpression could reverse this effect. All the data indicated that TET2 could demethylate TUG1 and contribute to the inflammatory response. In additional experiments using the MCAO mice model, we confirmed knockdown of TET2 attenuated I/R-induced inflammatory response and brain injuries via decreasing TUG1 and increasing miR-200a-3p to inhibit NLRP3 expression. The demethylation of TUG1 by TET2 might aggravate I/R-induced inflammatory injury via modulating NLRP3 by miR-200a-3p. Our data confirmed that TET2 contributed to I/R-induced inflammatory response via the demethylation of TUG1 and regulated TUG1/miR-200a-3p/NLRP3 pathway.
Exercise preconditioning reduces cerebral ischemia/reperfusion inflammatory injury in rats by the TLR4/NF-κB signaling pathway
