Proteome of Renal Tubuli and Serum Differentiate Pre-Existing Type 2 Diabetes and Post-Transplant Diabetes in Kidney Transplant Recipients.

IF 2.1 4区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

PROTEOMICS – Clinical Applications Pub Date : 2025-02-24 DOI:10.1002/prca.70000

Eleni Skandalou, Mariell Rivedal, Hans-Peter Marti, Thea A S Halden, Trond Jenssen, Bjørn Egil Vikse, Anders Åsberg, Jessica Furriol

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引用次数: 0

Abstract

Purpose: Diabetes mellitus (DM) is a major cause of end-stage kidney disease (ESKD), with kidney transplantation being the preferred treatment. However, post-transplant diabetes mellitus (PTDM) increases mortality and graft loss. While PTDM and Type 2 diabetes mellitus (T2DM) share risk factors, their mechanisms differ, particularly in diabetic nephropathy (DN). This study aimed to investigate the molecular differences in PTDM by mapping the proteomes of proximal tubuli and serum in normoglycemic (NG), pre-transplant T2DM, and PTDM patients one year post-transplantation. Experimental Design Proteomic analysis was performed on microdissected proximal tubular cells and serum samples from kidney transplant recipients categorized as NG, pre-transplant T2DM, or PTDM at one year post-transplantation. Mass spectrometry was used to identify differentially expressed proteins. Data analyses were performed using gene ontology databases and pathway analysis.

Results: Proteomic analysis revealed key differences, including significant dysregulation of mitochondrial proteins and lipid metabolism pathways in PTDM patients compared to T2DM and NG groups. Additionally, we observed distinct serum patterns of cholesterol metabolism dysregulation in PTDM, highlighting a complex interplay between fatty acid metabolism, mitochondrial dysfunction and systemic lipid dysregulation that may drive renal injury in PTDM-related DN.

Conclusions and clinical relevance: This pilot study is the first to perform proteomic analysis on both microdissected tubular cells and serum from post-transplant PTDM, pre-transplant T2DM and NG transplant recipients. The proteomic differences between PTDM and T2DM could help to develop targeted therapies and early diagnostic markers, ultimately improving transplant outcomes and patient management. Further research is needed to validate these findings and explore their therapeutic potential.

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来源期刊

PROTEOMICS – Clinical Applications 医学-生化研究方法

CiteScore

5.20

自引率

5.00%

发文量

审稿时长

1 months

期刊介绍： PROTEOMICS - Clinical Applications has developed into a key source of information in the field of applying proteomics to the study of human disease and translation to the clinic. With 12 issues per year, the journal will publish papers in all relevant areas including: -basic proteomic research designed to further understand the molecular mechanisms underlying dysfunction in human disease -the results of proteomic studies dedicated to the discovery and validation of diagnostic and prognostic disease biomarkers -the use of proteomics for the discovery of novel drug targets -the application of proteomics in the drug development pipeline -the use of proteomics as a component of clinical trials.