Antibody-validated proteins in inflamed islets of fulminant type 1 diabetes profiled by laser-capture microdissection followed by mass spectrometry.
Antibody-validated proteins in inflamed islets of fulminant type 1 diabetes profiled by laser-capture microdissection followed by mass spectrometry.
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DOI：
10.1371/journal.pone.0107664
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kobayashi T
中科院分区：
文献类型：
--
作者：
Nishida Y;Aida K;Kihara M;Kobayashi T
目前还没有1型糖尿病炎症胰岛蛋白质组学分析的报道。采用福尔马林固定石蜡包埋的胰腺组织，通过激光捕获显微切割质谱法鉴定肠病毒相关暴发性1型糖尿病（FT 1DM）伴广泛胰岛炎胰岛中表达的蛋白质。仅在FT 1DM胰岛中鉴定了38种蛋白质，其中大多数以前与1型糖尿病无关。鉴定了五个蛋白质-蛋白质相互作用簇，并对所选蛋白质的细胞定位进行了化学验证。在浸润到炎症FT 1DM胰岛的CD 8 + T细胞和CD 68+巨噬细胞中鉴定了迁移活性相关蛋白，包括plastin-2（LCP 1）、moesin（MSN）、lamin-B1（LMNB 1）、Ras GTP酶激活样蛋白（IQGAP 1）等。鉴定了参与先天/适应性免疫中的连续信号传导的蛋白质，包括SAM结构域和含HD结构域的蛋白1（SAMHD 1）、Ras GTP酶激活样蛋白（IQGAP 1）、蛋白酶体激活物复合物亚基1（PSME 1）、HLA I类组织相容性抗原（HLA-C）和信号转导和转录激活因子1-α/β（STAT 1）。在迁移性CD 8 + T细胞和CD 68+巨噬细胞中鉴定了血管生成（胸苷磷酸化酶（TYMP））和抗血管生成（T-tRNA连接酶（WARS））因子。与病毒复制和细胞增殖相关的蛋白质，包括可能的ATP依赖性RNA解旋酶DEAD盒解旋酶5（DDX 5）和异质核核糖核蛋白H（HNRNPH 1），被确定。在FT 1DM影响的胰岛细胞中鉴定了抗凋亡蛋白T-复合物蛋白1亚基（CCT 5）、抗氧化酶6-磷酸葡萄糖酸脱氢酶（PDG）、抗病毒和抗凋亡蛋白丝氨酸蛋白酶抑制剂B6（SERPINB 6）和热休克70 kDa蛋白1样（HSPA 1 L）。鉴定的FT 1DM特征蛋白包括通过大量免疫细胞迁移参与侵袭性β细胞破坏的蛋白，以及参与血管生成和胰岛血管出血、细胞修复和抗炎过程的蛋白。确定了未来1型糖尿病干预的几种靶蛋白。
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.
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影响因子：
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作者：
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