Shaoying Huang1, Fengping Zheng1, Hua Lin2, Xianqing Zhou2, Huixuan Xu1, Cantong Zhang1, Weier Dai3, Berthold Hocher4, Xinzhou Zhang5, Donge Tang6, Yong Dai7,8. 1. Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, 518020, Guangdong, People's Republic of China. 2. Guangxi Key Laboratory of Metabolic Disease Research, Nephrology Department of Guilin NO. 924 Hospital, Guilin, 541002, People's Republic of China. 3. College of Natural Science, University of Texas at Austin, Austin, Texas, 78712, USA. 4. Department of Medicine Nephrology, Medical Faculty Mannheim Heidelberg University, Mannheim, Germany. 5. Department of Nephrology, the Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, 518020, People's Republic of China. xinzhouzhang1946@163.com. 6. Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, 518020, Guangdong, People's Republic of China. donge66@126.com. 7. Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, 518020, Guangdong, People's Republic of China. daiyong22@aliyun.com. 8. Guangxi Key Laboratory of Metabolic Disease Research, Nephrology Department of Guilin NO. 924 Hospital, Guilin, 541002, People's Republic of China. daiyong22@aliyun.com.
Abstract
BACKGROUND: Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions. METHODS: In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins. CONCLUSIONS: Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN.
BACKGROUND: Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions. METHODS: In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin Anephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry. RESULTS: Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins. CONCLUSIONS: Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN.
Entities:
Keywords:
Immunoglobulin A nephropathy; Lysine 2-hydroxyisobutyrylation; Mass spectrometry; Peripheral blood mononuclear cells