Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus

Zhao Wen-Jing; Tan Rui-Zhi; He Si-Yuan; Du Xiao-Mei; Hu Qiong-Dan; Zhang Xiao-Qian; Huang Wen-Hua; Su Hong-Wei; Liu Jian; Zhang Qiong; Wang Li

doi:10.3389/fphys.2024.1287072

Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus

Front Physiol. 2024 Mar 21:15:1287072. doi: 10.3389/fphys.2024.1287072. eCollection 2024.

Authors

Zhao Wen-Jing^#^{1

2}, Tan Rui-Zhi^#¹, He Si-Yuan^#³, Du Xiao-Mei⁴, Hu Qiong-Dan^{1

4}, Zhang Xiao-Qian^{1

4}, Huang Wen-Hua³, Su Hong-Wei⁵, Liu Jian⁴, Zhang Qiong⁴, Wang Li¹

Affiliations

¹ Research Center of Intergated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China.
² Department of Nephrology, The Affiliated Hospital, Southwest Medical University, Luzhou, China.
³ School of Clinical Medicine, Southern Medical University, Guangzhou, China.
⁴ Department of Nephrology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China.
⁵ Department of Urology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China.

^# Contributed equally.

Abstract

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP.

Keywords: CKD; DEPs; data independent acquisition; proteomics; uremic pruritus.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Sichuan Science and Technology Program (2022YFS0621), the Luzhou-Southwest Medical University Science and Technology Strategic Cooperation Project (2021LZXNYD-P04), the Innovation Team of Affiliated Traditional Medicine Hospital of Southwest Medical University (2022-CXTD-03) and the Guangdong Province’s Science and Technology Innovation Strategy project (pdjh 2023b0109).