Dataset Information

Protein Lactylation modification and Proteomics Features in Cirrhosis Patients after MSCs Treatment.

ABSTRACT: Mesenchymal stem cell (MSC) therapy improves liver function in patients with liver cirrhosis. However, the therapeutic mechanism underlying MSC therapy remains unclear. Therefore, this study aimed to elucidate the therapeutic mechanism underlying MSC therapy by analyzing changes in the modification and expression of proteins 1-month post-treatment with MSCs. This prospective study included 11 patients with cirrhosis who received MSC injection in the First Hospital of Lanzhou University. The laboratory indexes before and after treatment were collected to evaluate the clinical treatment effect of MSCs, and peptide segments were extracted from liver tissue before and after treatment to revealed the protein expression and lactylation modification. Meanwhile, weighted gene co-expression network analysis was used to analyze co-expression protein modules and their relationship with clinical features. The patients with liver cirrhosis showed an improvement trend after receiving MSC treatment, specifically, the liver protein synthesis function was significantly improved and coagulation function was also significantly improved. Proteomics combined with lactic acid proteomics revealed 160 Lysine lactylation (Kla) sites of 119 proteins. The downregulated lactylated proteins were associated with metabolic processes. The upregulated lactylated proteins were involved in biological processes. The protein-based co-expression module was significantly related to alkaline phosphatase, total bilirubin (TBIL), indirect bilirubin (IBIL), direct bilirubin (DBIL), and ALB, and 10 proteins significantly related to ALB and 10 proteins significantly related to bilirubin were screened. The changes in clinical indexes before and after treatment indicate that the clinical effects of MSC treatment are related to cell metabolism. Overall, this study is the first study to comprehensively and systematically reveal the changes of lactylated proteins and expression after treatment with MSC by the self-control of patients, and lays a foundation for understanding the functions of lactylation modification in MSC therapy.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

SUBMITTER: ye xie

LAB HEAD: Xun Li

PROVIDER: PXD037530 | Pride | 2024-01-26

REPOSITORIES: pride

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Protein Lactylation Modification and Proteomics Features in Cirrhosis Patients after UC-MSC Treatment.

Xie Ye Y Li Ying Y Yao Jia J Song Xiaojing X Wang Haiping H Zhang Jianjun J Li Xun X

Current issues in molecular biology 20231018 10

Umbilical cord mesenchymal stem cell (UC-MSC) therapy improves liver function in liver cirrhosis patients. This study aimed to elucidate the therapeutic mechanism underlying cell therapy by analyzing changes in the modification and expression of proteins 1 month post-treatment with UC-MSCs. This prospective study included 11 cirrhosis patients who received MSC injection. The laboratory indexes before and after treatment were collected to evaluate the clinical treatment effect of UC-MSCs, and the ...[more]

PMID: 37886975

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Project description:Lysine lactylation (Kla) is a newly discovered histone post-translational modification (PTM), playing important roles in regulating transcription in macrophages. Increasing evidence demonstrates that lysine lactylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine lactylation in fungi, here investigated with the black yeast Phialophora verrucosaverrucose as a model organism. WeHere, we report the first proteomic survey of this modification in P. verrucosa. We performed a global lactylation analysis of P. verrucosa using high accuracy bottom-up nano-LC-MS/MS in combination wwith the enrichment of lactylated peptides from digested cell lysates and subsequent peptide identification. In total, 636 lactylation sites on 420 lactylated proteins were identified in this pathogen, of which contained in 26 types of modification motifs. Our results show that over 85% of lactylated proteins were distributed in cytoplasm, mitochondria, and nucleus. The identified proteins were found to be involved associated toin diverse biological processes and were significantly enriched in the melanin biosynthesis process. Most strikingly, Kla was found in 23 structural constituent proteins of ribosome, indicating an impact of Kla in protein synthesis . Moreover, 12 lactylated proteins participated in fungal pathogenicity, suggesting a potential role for Kla in this process. Protein interaction network analysis suggested that a mass of protein interactions are regulated by lactylation. Together, our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in P. verrucosa. Our data provide a rich resource for functional analyses of lactylation and facilitate the dissection of metabolic networks in this pathogen. The combined data sets represent the first report of the lactylome of P. verrucosa and provide a good foundation for further explorations of Kla in clinical fungal pathogens.

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