Protective role of TRPM7 knockdown in ulcerative colitis via blocking NLRP3 inflammasome-mediated pyroptosis.

Transient receptor potential melastatin 7 (TRPM7) has been emerged as a potent drug target for immunomodulation with ion conductance and kinase activities. The research is projected to characterize the influences of TRPM7 on the course of ulcerative colitis (UC) and dissect the latent response mechanisms. The in vivo murine model and in vitro cell model of UC were both stimulated by DSS. RT-qPCR and western blotting tested the abundance of TRPM7. Colonic damage was estimated by Hematoxylin-eosin staining, calculation of colon length, measurement of DAI and MPO assay kit. CCK-8 method and TUNEL staining severally ascertained cell activity and apoptosis. ELISA method assayed the inflammatory levels and relevant assay kits determined oxidative stress levels. FITC-dextran flux, immunohistochemistry, TEER as well as western blotting evaluated intestinal barrier function. Immunofluorescence staining and western blotting appraised NLR family pyrin domain containing 3 (NLRP3)-dependent pyroptosis. Depleted TRPM7 retarded inflammation, oxidative damage as well as intestinal barrier damage both in vitro and in vivo. TRPM7 reduction repressed the pyroptosis mediated by NLRP3 inflammasome. NLRP3 agonist nigericin partly abolished the protection elicited by TRPM7 silencing against inflammation, oxidative damage as well as intestinal barrier damage in vitro. Collectively, TRPM7 deletion might possess the therapeutic potential in UC, the working mechanism of which might involve the inactivation of NLRP3-dependent pyroptosis.