Peptide location fingerprinting identifies structural alterations within basement membrane components in ageing
Alexander Eckersley1, Mychel Rpt Morais2, Matiss Ozols3
1Division of Musculoskeletal & Dermatological Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK; Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Summary
Aging kidneys show changes in basement membrane proteins due to accumulated damage. Peptide location fingerprinting identified specific proteins and interactions altered by aging, offering potential therapeutic targets for kidney degeneration.
Area of Science:
- Proteomics and Mass Spectrometry
- Gerontology and Aging Research
- Renal Physiology and Pathology
Background:
- Kidney glomerular and tubular basement membranes (BM) decline functionally with age, marked by glomerulosclerosis and fibrosis.
- Age-related BM changes are linked to accumulated damage in long-lived extracellular matrix (ECM) proteins.
- Understanding BM protein susceptibility and consequences is key for age-related kidney disease research and therapies.
Purpose of the Study:
- To identify kidney basement membrane (BM) proteins with structure-associated differences between young and aged human kidney compartments.
- To investigate potential mechanisms and downstream consequences of age-dependent BM protein alterations.
- To utilize Peptide Location Fingerprinting (PLF) as a bioinformatic tool for screening ECM protein changes.
Main Methods:
- Application of Peptide Location Fingerprinting (PLF), a proteomic mass spectrometry technique.
- Analysis of human glomerular and tubulointerstitial compartments from young and aged individuals.
- Bioinformatic screening to detect structure-associated differences in BM proteins.
Main Results:
- Alterations in tryptic peptide yield were observed in functional regions of key BM components (e.g., agrin, laminins).
- Evidence of age-dependent shifts in molecular interactions, oxidation (collagen IV), and matrikine release (canstatin, endostatin) was found.
- Periostin and collagen IV α2 chain showed conserved age-related differences in human kidney and mouse lung.
Conclusions:
- PLF successfully identified BM proteins with age-associated structural differences in the human kidney.
- Specific BM components exhibit conserved age-related susceptibilities across species and organs, like periostin and collagen IV α2.
- Findings provide insights into age-related kidney degeneration mechanisms and potential biomarkers for therapeutic intervention.
