Abstract: TH-PO1072
Human Proximal Tubule Epithelial Cellular and Mitochondrial Proteome Significantly Varies by Sex and Age
Session Information
- Pathology and Lab Medicine
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1700 Pathology and Lab Medicine
Authors
- Hart, Brian R., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Wilkey, Daniel Wade, University of Louisville, Louisville, Kentucky, United States
- Gaweda, Adam E., University of Louisville, Louisville, Kentucky, United States
- Hata, Jessica Lynn, Atrium Health, Charlotte, North Carolina, United States
- Barati, Michelle T., University of Louisville, Louisville, Kentucky, United States
- Merchant, Michael, University of Louisville School of Medicine, Louisville, Kentucky, United States
Background
A prominent function of renal proximal tubule epithelial cells (PTEC) is solute reabsorption from glomerular filtrate and ion transport back into the blood. These functions are accomplished using apical and basolateral membrane-bound transporters including many associated with chronic kidney disease (CKD) and targeted by pharmaceuticals. Previous studies in rodents have shown sex (female, F; male, M)- and age-dependent transporter distribution in renal expression, but much less is known in humans. We hypothesized that the PTEC proteome would vary with sex- and age, and a spatial proteomics approach might reveal important differences enabling precision medicine approaches to guiding CKD management.
Methods
De-identified remnant kidney biopsy materials (n=12, 6-F/6-M) provided by a collaborating renal pathologist (UofL IRB 18.1319) were used for PTEC collection by laser-capture microdissection (LCM) and proteomic analysis by liquid chromatography-data independent acquisition mass spectrometry (LC-DIA-MS). Protein identifications were made using Spectronaut (v19.1). Differences were compared (a) categorically by two-way ANOVA and (b) continuously for age by Spearman correlation. Significance was defined by p<0.05 and q<0.05. Exploratory analysis included StringDB, HumanBase, and the KPMP Kidney Tissue Atlas. Confirmatory experiments used immunofluorescence (IF) microscopy.
Results
1,094 proteins were identified in all samples. Significant differences by 2-way ANOVA included: 81 by sex, 20 by age, and 18 by sex/age interaction. 120 proteins were significantly correlated to age: 15 unique to M and 76 unique to F. Regarding 18 transporter proteins observed: 2 were significant by age, 1 by sex, and 1 by their interaction. 4 transporters approached significance: 1 by age, 2 by sex, and 1 by their interaction. Pathways analysis identified enrichments in mitochondrial and membrane proteins including SGLT2. IF confirmation experiments document a significant age-dependent increase in PTEC ferritin light chain (FTL).
Conclusion
These results show the PTEC exhibits sex- and age-dependent changes in the spatial proteome including key transporter proteins. Striking differences in FTL expression suggest a role for iron metabolism in PTEC aging. Ongoing work seeks to (1) validate select targets that vary by sex and mitochondrial localization and (2) expand biologic replicates beyond discovery cohort.
Acknowledgment
Research supported by a grant from NIH T35 DK072923 and the University of Louisville School of Medicine Summer Research Scholar Program.
Funding
- NIDDK Support