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. 2024 Sep;67(9):1962-1979.
doi: 10.1007/s00125-024-06210-8. Epub 2024 Jul 22.

Spatial proteomics of human diabetic kidney disease, from health to class III

Ayano Kondo  1 , Monee McGrady  1 , Dhiraj Nallapothula #  2 , Hira Ali #  1 , Alexandro E Trevino  1 , Amy Lam  1 , Ryan Preska  1 , H Blaize D'Angio  1 , Zhenqin Wu  1 , Lauren N Lopez  2 , Harshanna K Badhesha  2 , Chenoa R Vargas  2 , Achyuta Ramesh  3 , Nasim Wiegley  2 , Seung Seok Han  4 , Marc Dall'Era  5 , Kuang-Yu Jen  6 , Aaron T Mayer  1 , Maryam Afkarian  7
Affiliations

Spatial proteomics of human diabetic kidney disease, from health to class III

Ayano Kondo et al. Diabetologia. 2024 Sep.

Abstract

Aims/hypothesis: Diabetic kidney disease (DKD) is the leading cause of chronic and end-stage kidney disease in the USA and worldwide. Animal models have taught us much about DKD mechanisms, but translation of this knowledge into treatments for human disease has been slowed by the lag in our molecular understanding of human DKD.

Methods: Using our Spatial TissuE Proteomics (STEP) pipeline (comprising curated human kidney tissues, multiplexed immunofluorescence and powerful analysis tools), we imaged and analysed the expression of 21 proteins in 23 tissue sections from individuals with diabetes and healthy kidneys (n=5), compared to those with DKDIIA, IIA-B and IIB (n=2 each) and DKDIII (n=1).

Results: These analyses revealed the existence of 11 cellular clusters (kidney compartments/cell types): podocytes, glomerular endothelial cells, proximal tubules, distal nephron, peritubular capillaries, blood vessels (endothelial cells and vascular smooth muscle cells), macrophages, myeloid cells, other CD45+ inflammatory cells, basement membrane and the interstitium. DKD progression was associated with co-localised increases in inflammatory cells and collagen IV deposition, with concomitant loss of native proteins of each nephron segment. Cell-type frequency and neighbourhood analyses highlighted a significant increase in inflammatory cells and their adjacency to tubular and αSMA+ (α-smooth muscle actin-positive) cells in DKD. Finally, DKD progression showed marked regional variability within single tissue sections, as well as inter-individual variability within each DKD class.

Conclusions/interpretation: Using the STEP pipeline, we found alterations in protein expression, cellular phenotypic composition and microenvironment structure with DKD progression, demonstrating the power of this pipeline to reveal the pathophysiology of human DKD.

Keywords: Diabetic kidney disease; Spatial biology; Tissue proteomics.

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References

    1. ElSayed NA, Aleppo G, Aroda VR et al (2023) 11. Chronic kidney disease and risk management: standards of care in diabetes – 2023. Diabetes Care 46(Suppl 1):S191–S202. https://doi.org/10.2337/dc23-S011 - DOI - PubMed
    1. Lewis SM, Asselin-Labat ML, Nguyen Q et al (2021) Spatial omics and multiplexed imaging to explore cancer biology. Nat Methods 18(9):997–1012. https://doi.org/10.1038/s41592-021-01203-6 - DOI - PubMed
    1. Hansen J, Sealfon R, Menon R et al (2022) A reference tissue atlas for the human kidney. Sci Adv 8(23):eabn4965. https://doi.org/10.1126/sciadv.abn4965 - DOI - PubMed - PMC
    1. Neumann EK, Patterson NH, Rivera ES et al (2022) Highly multiplexed immunofluorescence of the human kidney using co-detection by indexing. Kidney Int 101(1):137–143. https://doi.org/10.1016/j.kint.2021.08.033 - DOI - PubMed
    1. Hossain MS, Shahriar GM, Syeed MMM et al (2023) Region of interest (ROI) selection using vision transformer for automatic analysis using whole slide images. Sci Rep 13(1):11314. https://doi.org/10.1038/s41598-023-38109-6 - DOI - PubMed - PMC

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