Pancreatic Tissue Proteomics Unveils Key Proteins, Pathways, and Networks Associated with Type 1 Diabetes
Autor: | Qibin Zhang, Jongmin Woo, Putty-Reddy Sudhir |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Adult Male Proteomics Adolescent Proteome Clinical Biochemistry Quantitative proteomics Computational biology Collagen Type VI Biology Article Pathogenesis 03 medical and health sciences Young Adult medicine Humans Insulin Clinical significance Pancreas Type 1 diabetes geography geography.geographical_feature_category 030102 biochemistry & molecular biology medicine.disease Islet Carboxypeptidase B Isobaric labeling 030104 developmental biology Diabetes Mellitus Type 1 Case-Control Studies Female Biomarkers |
Zdroj: | Proteomics Clin Appl |
ISSN: | 1862-8354 |
Popis: | Purpose Type 1 diabetes (T1D) is characterized by autoimmune mediated self-destruction of the pancreatic islet beta cells and the resultant insulin deficiency. However, little is known about the underlying molecular pathogenesis at the pancreatic tissue level given the limited availability of clinical specimens. Experimental design We performed quantitative proteomic studies on age-matched T1D and healthy cadaveric pancreatic tissues (n = 18 each) using TMT 10plex-based isobaric labeling and BoxCar-based label-free LC-MS/MS approaches. ELISA was used to validate the differentially expressed proteins (DEPs). Results Overall, the two quantitative proteomics approaches identified 8,824 proteins, of which 261 were DEPs. KEGG pathway and functional network analyses of the DEPs revealed dysregulations to pancreatic exocrine function, complement coagulation cascades, and ECM receptor interaction pathways in T1D. A selected list of the DEPs associated with pathways, subnetworks, and plasma proteome of T1D were validated using ELISA. Conclusions and clinical relevance Integrating labeling and label-free approaches improved the confidence in quantitative profiling of pancreatic tissue proteome, which furthers our understanding of the dysregulated pathways and functional subnetworks associated with T1D pathogenesis and may aid to develop diagnostic and therapeutic strategies for T1D. This article is protected by copyright. All rights reserved. |
Databáze: | OpenAIRE |
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