Qualitative Proteome-wide Lysine Crotonylation Profiling Reveals Protein Modification Alteration in the Leukocyte Extravasation Pathway in Systemic Lupus Erythematosus

Huiyi Zeng; Dandan Li; Jingjing Dong; Xianqing Zhou; Minglin Ou; Wen Xue; Ruohan Zhang; Yaoshuang Zou; Donge Tang; Lianghong Yin; Yong Dai

doi:10.1021/acsomega.3c06293

Qualitative Proteome-wide Lysine Crotonylation Profiling Reveals Protein Modification Alteration in the Leukocyte Extravasation Pathway in Systemic Lupus Erythematosus

ACS Omega. 2023 Nov 14;8(47):44905-44919. doi: 10.1021/acsomega.3c06293. eCollection 2023 Nov 28.

Authors

Huiyi Zeng^{1

2}, Dandan Li^{1

3

4}, Jingjing Dong^{2

4}, Xianqing Zhou⁵, Minglin Ou⁵, Wen Xue⁵, Ruohan Zhang⁵, Yaoshuang Zou⁵, Donge Tang⁴, Lianghong Yin^{2

6}, Yong Dai^{4

5

1}

Affiliations

¹ The First Affiliated Hospital, School of Medicine, Anhui University of Science and Technology, Huainan, Anhui 232001, China.
² Institute of Nephrology and Blood Purification, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, China.
³ Experimental Center, Shenzhen Pingle Orthopedic Hospital (Shenzhen Pingshan Traditional Chinese Medicine Hospital), Shenzhen, Guangdong 518118, China.
⁴ Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, China.
⁵ Guangxi Key Laboratory of Metabolic Diseases Research, No. 924 Hospital of PLA Joint Logistic Support Force, Guilin, Guangxi 541002, China.
⁶ Huangpu Institute of Materials, Guangzhou, Guangdong 510663, China.

Abstract

Background: Systemic lupus erythematosus (SLE) is a severe systemic autoimmune disease with multiple manifestations. Lysine crotonylation (Kcr) is a newly discovered posttranslational modification epigenetic pattern that may affect gene expression and is linked to diseases causally.

Methods: We collected blood samples from 11 SLE individuals and 36 healthy subjects. Then, we used highly sensitive liquid chromatography-mass spectrometry technology to carry out proteomics and quantitative crotonylome analysis of SLE peripheral blood mononuclear cells in this investigation, which indicated the unique etiology of SLE. Finally, we verified the expression of critical protein in the leukocyte extravasation pathway by online database analysis and Western blot.

Results: There were 618 differentially expressed proteins (DEPs), and 612 crotonylated lysine sites for 272 differentially modified proteins (DMPs) found. These DEPs and DMPs are primarily enriched in the leukocyte extravasation signaling pathway, such as MMP8, MMP9, and ITGAM.

Conclusions: This is the first study of crotonylated modification proteomics in SLE. The leukocyte extravasation signaling pathway had a considerable concentration of DEPs and DMPs, indicating that this pathway may be involved in the pathogenic development of SLE.