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. 2021;145(6):760-769.
doi: 10.1159/000518424. Epub 2021 Sep 3.

The Landscape and Potential Regulatory Mechanism of Lysine 2-Hydroxyisobutyrylation of Protein in End-Stage Renal Disease

Fengping Zheng  1   2 , Huixuan Xu  3 , Shaoying Huang  3 , Cantong Zhang  3 , Shanshan Li  3 , Kang Wang  3 , Weier Dai  4 , Xinzhou Zhang  3 , Donge Tang  5 , Yong Dai  3   5
Affiliations

The Landscape and Potential Regulatory Mechanism of Lysine 2-Hydroxyisobutyrylation of Protein in End-Stage Renal Disease

Fengping Zheng et al. Nephron. 2021.

Abstract

Background: Acetylation has a vital role in the pathogenesis of end-stage renal disease (ESRD). Lysine 2-hydroxyisobutyrylation (Khib) is a novel type of acetylation. In this study, we aimed to reveal the key features of Khib in peripheral blood monocytes (PBMCs) of patients with ESRD.

Method: We combined TMT labeling with LC-MS/MS analysis to compare Khib 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 Khib, and the bioinformatics analysis was conducted to analyze the pathology of these Khib-modified proteins.

Result: Compared to healthy controls, we identified 440 upregulated proteins and 552 downregulated proteins in PBMCs of ESRD, among which 579 Khib sites on 324 upregulated proteins and 287 Khib sites on 188 downregulated proteins were identified. The site abundance, distribution, and function of the Khib 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.

Conclusion: In this study, we found that Khib-modified proteins correlated with the occurrence and progression of ESRD.

Keywords: End-stage renal disease; Liquid chromatography with tandem mass spectrometry; Lysine 2-hydroxyisobutyrylation; Renal fibrosis; Tandem mass tag labeling.

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