Project description:Lysine lactylation, a new post-translational modification identified on histones of human and mouse cells, stimulates gene transcription from chromatin directly. However, very little is known in the scope and cellular distribution of lactylated proteins. In the present study, we conducted the first proteome-wide survey of lactylated sites in Trypanosoma brucei, a unicellular parasite causing human African sleeping sickness and livestock nagana disease, using LC-MS/MS to identify peptides enriched by immuno-purification with an anti-lactyllysine antibody. Overall, we identified 387 unique lysine lactylated sites in 257 lactylated proteins with diverse cellular localizations and biological functions. Lactylated proteins are involved in a wide variety of cellular functions such as metabolism and gene regulation. Further, we demonstrate that the lactate-derived lactylation in trypanosome is regulated by glucose metabolism. Collectively, our findings provide the first comprehensive view of the lactylome of T. brucei and suggest that lysine lactylation in trypanosomes involves a diverse array of cellular functions.
Project description:Porcine cytomegalovirus (PCMV; genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae) is an immunosuppressive virus that mainly inhibits the immune function of T lymphocytes and macrophages, which has caused great distress to the farming industry. In this study, we obtained the miRNA expression profiles of PCMV-infected and control porcine macrophages, PCMV-infected and control porcine tissues via high-throughput sequencing. The comprehensive analysis of miRNA profiles showed that 306 miRNA database annotated and 295 novel pig-encoded miRNAs were detected. Gene Ontology (GO) analysis of the target genes of miRNAs in PCMV infected porcine macrophages showed that the differentially expressed miRNAs are mainly involved in immune and metabolic process. This is the first report of the miRNA transcriptome in PCMV infected porcine macrophages and PCMV infected tissues and the analysis of the miRNA regulatory mechanism during PCMV infection. Further research into the regulatory mechanisms of miRNAs during immunosuppressive viral infections will contribute to the treatment and prevention of immunosuppressive viruses.
Project description:Porcine cytomegalovirus (PCMV; genus Cytomegalovirus, subfamily Betaherpesvirinae, family Herpesviridae) is an immunosuppressive virus that mainly inhibits the immune function of T lymphocytes and macrophages, which has caused great distress to the farming industry. In this study, we obtained the miRNA expression profiles of PCMV-infected and control porcine macrophages, PCMV-infected and control porcine tissues via high-throughput sequencing. The comprehensive analysis of miRNA profiles showed that 306 miRNA database annotated and 295 novel pig-encoded miRNAs were detected. Gene Ontology (GO) analysis of the target genes of miRNAs in PCMV infected porcine macrophages showed that the differentially expressed miRNAs are mainly involved in immune and metabolic process. This is the first report of the miRNA transcriptome in PCMV infected porcine macrophages and PCMV infected tissues and the analysis of the miRNA regulatory mechanism during PCMV infection. Further research into the regulatory mechanisms of miRNAs during immunosuppressive viral infections will contribute to the treatment and prevention of immunosuppressive viruses. miRNA expression profiling of PCMV-infected and control porcine macrophages; PCMV-infected and control porcine tissues via high-throughput sequencing.
Project description:To gain a more complete understanding of how porcine cathelicidin PR-39 influence the porcine intestinal epithelial cells, we profiled gene expression patterns in IPEC-J2 cell line in the presence or the absence of PR-39.
Project description:<p>Interstitial renal inflammation contributes to the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). Recently, protein lactylation modification has emerged as a novel mechanism for mediating chronic organ damage. We investigated lactylated protein profiles and the role of protein lactylation during AKI progression. Severe and moderate AKI mouse models were constructed by bilateral renal ischemia for 35 and 25 min, respectively. Lactylation enhancers and inhibitors were used to verify the effect of protein lactylation. Lactylated proteomics was used to detect lactylated protein changes in kidneys, and the lactylated proteins related to kidney injury were screened for verification. We observed significantly higher lactate and protein lactylation levels in the severe AKI model than in the moderate AKI model 1-28 days post-injury. Inhibition of protein lactylation protects against renal interstitial fibrosis. In vitro and in vivo experiments demonstrated that protein lactylation activated Nod-like receptor protein 3 (NLRP3) inflammasomes, promoting the AKI-CKD transition. Comprehensive lactylome profiling of severe AKI models revealed a role for lactylated proteins in metabolic pathways, primarily the tricarboxylic acid (TCA) cycle, where the rate-limiting enzyme, citrate synthase (CS), exhibited significantly elevated lactylation levels 3-7 days post-AKI induction; K370 was the most significant lysine residue. In vitro, following hypoxia/reoxygenation, the modified/lactylated K370T group significantly decreased CS activity and mitochondrial function. Furthermore, CS-K370 lactylation activated the NLRP3 inflammasomes. Thus, lactylation of CS promotes the AKI-CKD transition through NLRP3 inflammasome activation. Inhibition of CS lactylation shows therapeutic potential for preventing this transition.</p>