The inhibition of HACE1 ameliorates inflammatory responses in citrobacter rodentium-induced murine colitis through Nrf2/ NLRP3 signaling pathway

Abstract

This study was intended to elucidate the effects of HACE1 in Citrobacter rodentium-Induced Murine Colitis. Male C57BL/6 mice orally administered with 100 µLof Citrobacter rodentium DBS-100 (109 CFU mL⁻¹) for 14 days. The expression of HACE1 in Citrobacter rodentium-Induced Murine Colitis was increased. HACE1 promoted inflammation and ROS levels in macrophage through the inactivation of Nrf2/NLRP3 signaling pathway. Meanwhile, si-HACE1 reduced inflammation and ROS levels in macrophage via the inhibition of Nrf2/NLRP3 signaling pathway. Sh-HACE1 reduced inflammatory responses in Citrobacter rodentium-Induced Murine Colitis through the promotion of Nrf2/NLRP3 signaling pathway. IP showed that HACE1 protein catenated with Nrf2 protein to suppress ROS-induced NLRP3 in macrophage through the promotion of Nrf2 Ubiquitination. Altogether, our data demonstrate that the inhibition of HACE1 ameliorates

inflammatory responses in Citrobacter rodentium-induced Murine Colitis through the inhibition of ROS-induced mitochondrial damage by Nrf2/NLRP3. m6A promoted HACE1 stability by METTL3. Our study revealed the m6A methyltransferase METTL3 promoted HACE1 stability to promote NLRP3 activity in Citrobacter rodentium-Induced Murine Colitis by the inhibition of Nrf2.

Keywords:
HACE1; NLRP3; m6A; METTL3; colitis