Deferoxamine preconditioning activated hypoxia-inducible factor-1α and MyD88-dependent Toll-like receptor 4 signaling in intestinal stem cells

摘要: Abstract Background/Purpose Toll-like receptors (TLRs) are important regulators of innate immunity, and TLR4 pathway can regulate the survival, migration, differentiation stem cells, including intestinal cells (ISCs). Deferoxamine (DFO), a hypoxia-mimic compound, activate proliferation ISCs. In this study, we investigated response signaling to DFO-induced hypoxia in cultured ISCs vitro . Methods After DFO treatment, crypt organoid number was counted, expression levels Lgr5, Hsp70, HMGB1, HIF-1α, TLR4, MyD88, TRIF, TRAM were examined using QPCR Western blotting. The chemical inhibitors different molecules then used determine their role change Results TRIF increased after with peak these 6h treatment. addition, gene Lgr5 HIF-1α partially reversed by pretreatment inhibitor or but not inhibitor. Inhibition also resulted partial downregulation elevation TLR4. Conclusions These results demonstrated that treatment activated TLR4-MyD88 pathway, which might mediate activation