Antibody-Validated Proteins in Inflamed Islets of Fulminant Type 1 Diabetes Profiled by Laser-Capture Microdissection Followed by Mass SpectrometryReportar como inadecuado

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There are no reports of proteomic analyses of inflamed islets in type 1 diabetes.


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.


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.


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.

Autor: Yoriko Nishida, Kaoru Aida, Makoto Kihara, Tetsuro Kobayashi



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