METHYLTRANSFERASE SMYD5 EXAGGERATES INFLAMMATORY BOWEL DISEASE BY REGULATING PPAR-γ COACTIVATOR 1-α STABILITY

Abstract Background and Aims The expression role of methyltransferase SET MYND domain-containing protein 5 (SMYD5) in inflammatory bowel diseases (IBD) is completely unknown. Here, we investigated the underlying mechanism epithelial SMYD5 IBD pathogenesis progression. Methods subcellular localization peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) were examined by Western blot analysis, immunofluorescence staining, immunohistochemistry intestinal cells (IECs) colon tissues from human patients mice with experimental colitis. Mice Smyd5 conditional knockout IECs littermate controls subjected to DSS-induced colitis disease severity inflammation assessed. SMYD5-regulated mitochondrial biogenesis was RT-qPCR transmission electron microscopy oxygen consumption rate measured a Seahorse Analyzer system. interaction between PGC-1α determined co-immunoprecipitation assay. degradation turnover (half-life) analyzed cycloheximide chase SMYD5-mediated methylation via vitro followed mass spectrometry identify specific lysine residues that methylated. Results Up-regulated down-regulated observed However, depletion protected critically involved regulating biology such as biogenesis, respiration, apoptosis. Mechanistically, regulated functions dependent manner. Further, mediated facilitated its ubiquitination proteasomal degradation. Conclusion attenuates promotes progression enhancing proteasome-mediated methylation-dependent Strategies decrease and/or increase might be promising therapeutic approach treat IBD.