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The following is a summary of “Protein N-glycans in Healthy and Sclerotic Glomeruli in Diabetic Kidney Disease,” published in the May 2024 issue of Nephrology by Veličković et al.

Diabetes is known to affect kidney glycosylation, but there hasn’t been a thorough study on how N-glycan composition changes in the glomeruli of people with diabetic kidney disease (DKD). 

Researchers conducted a retrospective study to investigate the alterations in N-glycan composition in the glomeruli of patients with DKD. 

They used untargeted mass spectrometry imaging to identify N-glycan structures in healthy and sclerotic glomeruli from kidney biopsies of 5 patients with DKD and 3 healthy samples. Regional proteomics compared enzyme levels in glycosylation, and single nuclei transcriptomics (snRNAseq) data analyzed glycosylation machinery transcripts in different cell types and states. 

The results showed that 120 N-glycans, with 12 of these protein post-translated modifications, significantly increased in glomeruli. All glomeruli-specific N-glycans had an N-acetyllactosamine (LacNAc) epitope. Only 5 N-glycans structure distinguished sclerotic from healthy glomeruli. Sclerotic glomeruli lacked fucose-linked glycans and tetra-antennary structures. Orthogonal omics showed lower protein and gene expression for fucosylated and branched N-glycans in sclerotic podocytes. In snRNAseq and regional proteomics analyses, genes and proteins for sialylation and LacNAc synthesis were downregulated in DKD glomeruli, though not detected by spatial N-glycomics assay.

Investigators concluded that combining spatial glycomics, proteomics, and transcriptomics showed distinct protein N-glycosylation patterns of sclerotic glomeruli in DKD.

Source: journals.lww.com/jasn/abstract/9900/protein_n_glycans_in_healthy_and_sclerotic.327.aspx