Spatial proteomics to discover aging-associated alterations in the renal tubulointerstitium

ABSTRACT: The preservation of tissue architecture and morphology, in formalin-fixed paraffin-embedded (FFPE) tissue enables spatial resolution at the cellular and sub-cellular level. Laser capture microdissection (LCM) combined with liquid chromatography mass spectrometry analysis has enabled the collection of tissue areas within a spatial context for proteome profiling of FFPE tissues. In this study, we performed proteome profiling of the renal normal tubulointerstitial tissue among cohorts of young (<40 years) and old (>70 years) individuals aiming to spatially correlating with these microstructural features to proteome profile. To gain in-depth understanding of kidney tubulointerstitial tissue and identify renal aging-associated proteins, a multiplexing strategy using tandem mass tag was employed, resulting in the quantitation of 7,371 proteins. We demonstrated that our approach allowed for identification kidney specific proteins with low abundance such as fibrocystin. In addition, 162 solute carrier proteins from 47 solute carrier families were identified, which are enriched in proximal and distal tubule cells. Finally, we discovered proteomic signature associated with renal aging, which includes metalloproteinase inhibitor 3, matrix metallopeptidase 7, phospholipase A2 group IIA, cytokine receptor like factor 1 and solute carrier family 23 member 1. Overall, we demonstrated the power of LCM combined with proteomics to leverage archived FFPE tissue samples to investigate renal aging because of its adaptability and sample backed compatibility.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney

SUBMITTER: Akhilesh Pandey  

LAB HEAD: Akhilesh Pandey

PROVIDER: PXD059176 | Pride | 2025-10-20

REPOSITORIES: Pride