Protein Glycosylation in Diabetes

Štambuk, Tamara; Gornik, Olga

doi:10.1007/978-3-030-70115-4_14

Cited by 10 publications

(8 citation statements)

References 113 publications

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“…(3) Complex carbohydrates are critical structural metabolites for cell-cell adhesion, signaling, and extracellular matrix remodeling 14 , 64 . (4) Aberrant complex carbohydrate metabolism drives pathogenesis in multiple human diseases including neurodegeneration 65 , 66 , type II diabetes 67 , cardiovascular disease 68 , and several types of cancer 69 , 70 . In this study, we demonstrate HDR-SC and biomarker prediction using spatial metabolomics datasets.…”

Section: Discussionmentioning

confidence: 99%

Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

et al. 2023

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Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases.

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Section: Discussionmentioning

confidence: 99%

Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

et al. 2023

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“…Galnt3, a member of the GalNAc-transferase family, initiates the O-glycosylation of proteins by transferring N-acetyl-D-galactosamine to hydroxyl groups of the side chains of Ser/Thr residues. 33,34 Mucin O-glycosylation, which represents the widest diversity of glycosylation, plays an important role in various biological processes, including immunity, homeostasis, and metabolism. 35,36 Thus, Galnt3 dysregulation results in the modulation of protein functions and the development of associated diseases.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin induces acute kidney injury by downregulating miR‐30e‐5p that targets Galnt3 to activate the AMPK signaling pathway

Mao,

Zhang,

Wang

et al. 2023

Environmental Toxicology

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Cisplatin nephrotoxicity is an etiological factor for acute kidney injury (AKI). MicroRNA (miRNA) expression is dysregulated in cisplatin‐induced AKI (cAKI) although the underlying mechanisms are unclear. A cAKI model was established by intraperitoneally injecting cisplatin, and key miRNAs were screened using high‐throughput miRNA sequencing. The functions of key miRNAs were determined using the cell viability, live/dead, reactive oxygen species (ROS), and 5‐ethynyl‐2′‐deoxyuridine (EdU) proliferation assays. Additionally, the macrophage membrane was wrapped around a metal–organic framework (MOF) loaded with miRNA agomir to develop a novel composite material, macrophage/MOF/miRNA agomir nanoparticles (MMA NPs). High‐throughput miRNA sequencing revealed that miR‐30e‐5p is a key miRNA that is downregulated in cAKI. The results of in vitro experiments demonstrated that miR‐30e‐5p overexpression partially suppressed the cisplatin‐induced or lipopolysaccharide (LPS)‐induced downregulation of cell viability, proliferation, upregulation of ROS production, and cell death. Meanwhile, the results of in vivo and in vitro experiments demonstrated that MMA NPs alleviated cAKI by exerting anti‐inflammatory effects. Mechanistically, cisplatin downregulates the expression of miR‐30e‐5p, and the downregulated miR‐30e‐5p can target Galnt3 to activate the adenosine 5‘‐monophosphate activated protein kinase (AMPK) signaling pathway, which promotes the progression of AKI. Our study found that miR‐30e‐5p is a key downregulated miRNA in cAKI. The downregulated miR‐30e‐5p promotes AKI progression by targeting Galnt3 to activate the AMPK signaling pathway. The newly developed MMA NPs were found to have protective effects on cAKI, suggesting a potential novel strategy for preventing cAKI.

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“…Glycosylation is one of the most abundant and diverse protein post-translational modifications in eukaryotes, with profound effects on protein function, stability, subcellular localization and other traits [14]. N-glycosylation, the main form of protein glycosylation, was dysregulated in common diseases such as cancer [15][16][17], inflammation [18], Alzheimer's disease [19,20] and diabetes [21][22][23]. Connor A West et al reported that the levels of tetra-antennary and fucosylation was elevated in HCC tissues compared to either cirrhotic tissue or adjacent untransformed tissue [24].…”

Section: Introductionmentioning

confidence: 99%

Integrating transcriptomics, glycomics and glycoproteomics to characterize hepatitis B virus-associated hepatocellular carcinoma

Li,

Zhang,

Dong

et al. 2024

Cell Commun Signal

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Background Hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker. Methods An integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC. Results Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis. Conclusions The findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression.

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Protein Glycosylation in Diabetes

Cited by 10 publications

References 113 publications

Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

Cisplatin induces acute kidney injury by downregulating miR‐30e‐5p that targets Galnt3 to activate the AMPK signaling pathway

Integrating transcriptomics, glycomics and glycoproteomics to characterize hepatitis B virus-associated hepatocellular carcinoma

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