Proteomic insights into age-related changes in laser capture microdissected glomeruli of human kidney

ABSTRACT: Kidney aging is characterized by loss of glomeruli, predominately in the superficial cortex, with a resultant decline in glomerular filtration rate and an increased risk of various kidney-related diseases. The early molecular alterations in glomeruli with the aging process is not well studied. In this study, we combined laser capture microdissection and mass spectrometry-based unbiased proteomic analysis of non-sclerosed, non-ischemic glomeruli in the superficial cortex from young and old individuals who underwent a radical nephrectomy for a tumor to understand the age-related molecular changes in glomeruli. As expected, kidneys from older individuals had lower eGFR, less total kidney cortex, more glomerulosclerosis, and more arteriosclerosis. Quantitative proteomic analysis showed several proteins involved in the extracellular matrix reorganization as over expressed in old compared to young individuals. Functional characterization of the differential expressed proteins showed that overexpressed proteins were enriched in mitochondrial translation elongation and termination whereas under expressed proteins were enriched in RNA splicing, mRNA transport and protein processing. Overexpression of TIMP3, APOA4, SNCG, NT5E and GPC6 were further confirmed by proteomic analysis on an independent cohort. After adjusting for age, expression of these proteins did not associate with low eGFR or chronic changes on histology or CT imaging of the kidneys. Overall, this study identified proteins that are associated with the normal aging process in otherwise normal appearing glomeruli.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney

DISEASE(S): Disease Free

SUBMITTER: Akhilesh Pandey  

LAB HEAD: Akhilesh Pandey

PROVIDER: PXD061392 | Pride | 2025-12-22

REPOSITORIES: Pride