The Landscape and Potential Regulatory Mechanism of Lysine 2-Hydroxyisobutyrylation of Protein in End-Stage Renal Disease
<b><i>Background:</i></b> Acetylation has a vital role in the pathogenesis of end-stage renal disease (ESRD). Lysine 2-hydroxyisobutyrylation (<i>K</i><sub>hib</sub>) is a novel type of acetylation. In this study, we aimed to reveal the key features of <i>K</i><sub>hib</sub> in peripheral blood monocytes (PBMCs) of patients with ESRD. <b><i>Method:</i></b> We combined TMT labeling with LC-MS/MS analysis to compare <i>K</i><sub>hib</sub> modification of PBMCs between 20 ESRD patients and 20 healthy controls. The pan 2-hydroxyisobutyrylation antibody-based affinity enrichment method was used to reveal the features of <i>K</i><sub>hib</sub>, and the bioinformatics analysis was conducted to analyze the pathology of these <i>K</i><sub>hib</sub>-modified proteins. <b><i>Result:</i></b> Compared to healthy controls, we identified 440 upregulated proteins and 552 downregulated proteins in PBMCs of ESRD, among which 579 <i>K</i><sub>hib</sub> sites on 324 upregulated proteins and 287 <i>K</i><sub>hib</sub> sites on 188 downregulated proteins were identified. The site abundance, distribution, and function of the <i>K</i><sub>hib</sub> protein were further analyzed. The bioinformatics analysis revealed that the Rho/ROCK signaling pathway was highly enriched in ESRD, suggesting that it might contribute to renal fibrosis in ESRD patients. <b><i>Conclusion:</i></b> In this study, we found that <i>K</i><sub>hib</sub>-modified proteins correlated with the occurrence and progression of ESRD.