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

Abstract

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 protein expression and lactylation modification in the liver were comprehensively revealed. Meanwhile, weighted gene co-expression network analysis was used to analyze the co-expression protein modules and their relationship with clinical features. The patients with liver cirrhosis showed an improvement trend after receiving UC-MSC treatment; specifically, the liver protein synthesis function was significantly improved and the coagulation function was also significantly improved. Proteomics combined with lactic acid proteomics revealed 160 lysine lactylation (Kla) sites of 119 proteins. Functional analysis showed that the lactylation-modified proteins were enriched in the pathway of glucose and other substances’ metabolism, and many key enzymes of glycolysis and gluconeogenesis were lactated. UC-MSC therapy has a certain clinical effect in the treatment of liver cirrhosis and may act by regulating material metabolism, because the lactylation protein points to energy metabolism.