Antibody-validated proteins in inflamed islets of fulminant type 1 diabetes profiled by laser-capture microdissection followed by mass spectrometry
| العنوان: | Antibody-validated proteins in inflamed islets of fulminant type 1 diabetes profiled by laser-capture microdissection followed by mass spectrometry |
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| المؤلفون: | Kaoru Aida, Makoto Kihara, Tetsuro Kobayashi, Yoriko Nishida |
| المصدر: | PLoS ONE PLoS ONE, Vol 9, Iss 10, p e107664 (2014) |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, Proteomics, Pathology, Tissue Fixation, endocrine system diseases, Fulminant, lcsh:Medicine, Protein Sequencing, Biochemistry, Mass Spectrometry, Analytical Chemistry, Endocrinology, Medicine and Health Sciences, Protein Interaction Maps, lcsh:Science, Laser capture microdissection, Innate Immune System, Microscopy, Multidisciplinary, geography.geographical_feature_category, Paraffin Embedding, Immune System Proteins, Chemotaxis, Infectious Disease Immunology, Islet, Cell Motility, Chemistry, medicine.anatomical_structure, Infectious Diseases, Physical Sciences, Antibody, Chemokines, Pancreas, Sequence Analysis, Research Article, Adult, endocrine system, medicine.medical_specialty, Adolescent, Immunology, Laser Capture Microdissection, Cell Migration, Immunopathology, Biology, Research and Analysis Methods, Antibodies, Islets of Langerhans, Diabetes mellitus, medicine, Humans, Molecular Biology Techniques, Sequencing Techniques, Molecular Biology, Immunohistochemistry Techniques, Inflammation, Diabetic Endocrinology, Type 1 diabetes, geography, lcsh:R, Biology and Life Sciences, Proteins, Cell Biology, medicine.disease, Histochemistry and Cytochemistry Techniques, Diabetes Mellitus, Type 1, Immune System, biology.protein, lcsh:Q, Clinical Immunology, Clinical Medicine |
| الوصف: | Background There are no reports of proteomic analyses of inflamed islets in type 1 diabetes. Procedures Proteins expressed in the islets of enterovirus-associated fulminant type 1 diabetes (FT1DM) with extensive insulitis were identified by laser-capture microdissection mass spectrometry using formalin-fixed paraffin-embedded pancreatic tissues. Results Thirty-eight proteins were identified solely in FT1DM islets, most of which have not been previously linked to type 1 diabetes. Five protein-protein interacting clusters were identified, and the cellular localization of selected proteins was validated immunohistochemically. Migratory activity-related proteins, including plastin-2 (LCP1), moesin (MSN), lamin-B1 (LMNB1), Ras GTPase-activating-like protein (IQGAP1) and others, were identified in CD8+ T cells and CD68+ macrophages infiltrated to inflamed FT1DM islets. Proteins involved in successive signaling in innate/adaptive immunity were identified, including SAM domain and HD domain-containing protein 1 (SAMHD1), Ras GTPase-activating-like protein (IQGAP1), proteasome activator complex subunit 1 (PSME1), HLA class I histocompatibility antigen (HLA-C), and signal transducer and activator of transcription 1-alpha/beta (STAT1). Angiogenic (thymidine phosphorylase (TYMP)) and anti-angiogenic (tryptophan-tRNA ligase (WARS)) factors were identified in migrating CD8+ T cells and CD68+ macrophages. Proteins related to virus replication and cell proliferation, including probable ATP-dependent RNA helicase DEAD box helicase 5 (DDX5) and heterogeneous nuclear ribonucleoprotein H (HNRNPH1), were identified. The anti-apoptotic protein T-complex protein 1 subunit epsilon (CCT5), the anti-oxidative enzyme 6-phosphogluconate dehydrogenase (PDG), and the anti-viral and anti-apoptotic proteins serpin B6 (SERPINB6) and heat shock 70 kDa protein1-like (HSPA1L), were identified in FT1DM-affected islet cells. Conclusion The identified FT1DM-characterizing proteins include those involved in aggressive beta cell destruction through massive immune cell migration and proteins involved in angiogenesis and islet vasculature bleeding, cell repair, and anti-inflammatory processes. Several target proteins for future type 1 diabetes interventions were identified. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5129f7c4d42c5014429e588b838e1d67Test https://pubmed.ncbi.nlm.nih.gov/25329145Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5129f7c4d42c5014429e588b838e1d67 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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