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. 2021 Nov 11;11(11):1677.
doi: 10.3390/biom11111677.

Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases

Aiying Yu  1 , Jingfu Zhao  1 , Shiv Pratap S Yadav  2 , Bruce A Molitoris  2 , Mark C Wagner  2 , Yehia Mechref  1
Affiliations

Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases

Aiying Yu et al. Biomolecules. .

Abstract

Chronic kidney disease (CKD) is defined by a reduced renal function i.e., glomerular filtration rate (GFR), and the presence of kidney damage is determined by measurement of proteinuria or albuminuria. Albuminuria increases with age and can result from glomerular and/or proximal tubule (PT) alterations. Brush-border membranes (BBMs) on PT cells play an important role in maintaining the stability of PT functions. The PT BBM, a highly dynamic, organized, specialized membrane, contains a variety of glycoproteins required for the functions of PT. Since protein glycosylation regulates many protein functions, the alteration of glycosylation due to the glycan changes has attracted more interests for a variety of disease studies recently. In this work, liquid chromatography-tandem mass spectrometry was utilized to analyze the abundances of permethylated glycans from rats under control to mild CKD, severe CKD, and diabetic conditions. The most significant differences were observed in sialylation level with the highest present in the severe CKD and diabetic groups. Moreover, high mannose N-glycans was enriched in the CKD BBMs. Characterization of all the BBM N-glycan changes supports that these changes are likely to impact the functional properties of the dynamic PT BBM. Further, these changes may lead to the potential discovery of glycan biomarkers for improved CKD diagnosis and new avenues for therapeutic treatments.

Keywords: LC-MS/MS; brush-border membrane; chronic kidney disease; glycomics; obese and diabetic; proteinuria and hypertension.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Unsupervised PCA of the BBMs N-glycans from five sample groups. Symbols with same color and shape were the replicates from same sample group. (b) Unsupervised PCA of the BBM N-glycans from old male with proteinuria and hypertension (G3) and young male control (G4). (c) Unsupervised PCA of the BBM N-glycans from male control (G4) and obese and diabetic male (G5). G3 were MWF male rats (32–42 weeks), G4 were MWF male rats (7 weeks), and G5 were ZSF1 male rats (16 weeks).
Figure 2
Figure 2
Box plot for relative abundance of 19 significant N-glycans (p < 0.0004) between old male with proteinuria and hypertension (G3) and young male control (G4). The putative structure was assigned to each glycan composition. The X axis denotes the four-digit codes for N-glycan compositions. The Y axis is the relative abundance. The four-digit codes represent N-glycan compositions. X-X-X-X stands for HexNAc-Hexose-DeoxyHex-NeuAc. HexNAc includes N-acetylglucosamine and N-acetylgalactosamine. Hexose includes galactose and mannose. Deoxyhexose is fucose and NeuAc is N-acetylneuraminic acid. Symbols:, N-acetylglucosamine (GlcNAc);, Galactose (Gal);, Fucose (Fuc);, Mannose (Man);, Glucose (Glc);, N-acetylneuraminic acid (NeuAc/Sialic Acid).
Figure 3
Figure 3
Distribution changes of different N-glycan types from (a) young male control (G4) and (b) old male with proteinuria and hypertension (G3); (c) Heatmap of 19 N-glycans that exhibited significant expression changes between G3 and G4. In the heatmap, each row represents an individual significant N-glycan. The red color of the cell denotes a high relative abundance, while the green color represents a low relative abundance of the N-glycan.
Figure 4
Figure 4
Box plot for relative abundance of 25 significant N-glycans (p < 0.0004) between young male control (G4) and obese and diabetic male (G5). The putative structure was assigned to each glycan composition. The X axis denotes the four-digit codes for N-glycan compositions. The Y axis is the relative abundance. Symbols: see Figure 2.
Figure 5
Figure 5
Distribution changes of different N-glycan types from (a) young male control (G4) and (b) obese and diabetic male (G5); (c) Heatmap of 25 N-glycans that exhibited significant expression changes between G4 and G5. In the heatmap, each row represents an individual significant N-glycan. The red color of the cell denotes a high relative abundance, while the green color represents a low relative abundance of the N-glycan.
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