Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes
Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes
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DOI：
10.1371/journal.pone.0135663
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发表时间：
2015-08-24
期刊：
影响因子：
3.7
通讯作者：
Nyalwidhe, Julius O.
中科院分区：
文献类型：
--
作者：
Burch, Tanya C.;Morris, Margaret A.;Nyalwidhe, Julius O.
1型糖尿病（T1D）和2型糖尿病（T2D）与由于持续炎症导致的功能性β细胞损失相关。尽管有共同的相似之处，T1D是一种自身免疫性疾病，有证据表明自身抗体的产生，以及胰腺外分泌的参与。我们的假设是，差异蛋白质表达发生在疾病分层胰腺组织和调节蛋白质的内分泌和外分泌组织是潜在的疾病标志物和潜在的治疗靶点。本研究的目的是鉴定新的蛋白质，以区分胰腺与T1D供体，胰腺与T2D患者，或自身抗体阳性的非糖尿病供体。详细的定量综合蛋白质组学分析应用于快速冷冻的人胰腺组织裂解物，这些组织来自无糖尿病的器官供体、在无糖尿病的情况下具有T1D相关自身抗体的器官供体、具有T1D的器官供体或具有T2D的器官供体。这些疾病分层的人胰腺组织在相同的微环境中包含外分泌和内分泌组织（具有功能失调的胰岛）。通过Western blot进一步验证了几种蛋白的表达谱。我们鉴定了与非疾病对照组织相比在三种疾病分层的胰腺组织中显著且独特地上调的蛋白质组。这些蛋白质参与炎症、代谢调节和自身免疫，所有这些都是与T1和T2糖尿病发病机制相关并可能参与其中的途径。几种新的蛋白质在糖尿病前期、T1D和T2D胰腺中差异性上调。结果确定了可以作为新的预后，诊断和治疗工具的蛋白质，以保持1型糖尿病的功能性胰岛质量。
Type 1 diabetes (T1D) and type 2 diabetes (T2D) are associated with functional beta cell loss due to ongoing inflammation. Despite shared similarities, T1D is an autoimmune disease with evidence of autoantibody production, as well as a role for exocrine pancreas involvement. Our hypothesis is that differential protein expression occurs in disease stratified pancreas tissues and regulated proteins from endocrine and exocrine tissues are potential markers of disease and potential therapeutic targets. The study objective was to identify novel proteins that distinguish the pancreas from donors with T1D from the pancreas from patients with T2D, or autoantibody positive non-diabetic donors. Detailed quantitative comprehensive proteomic analysis was applied to snap frozen human pancreatic tissue lysates from organ donors without diabetes, with T1D-associated autoantibodies in the absence of diabetes, with T1D, or with T2D. These disease-stratified human pancreas tissues contain exocrine and endocrine tissues (with dysfunctional islets) in the same microenvironment. The expression profiles of several of the proteins were further verified by western blot. We identified protein panels that are significantly and uniquely upregulated in the three disease-stratified pancreas tissues compared to non-disease control tissues. These proteins are involved in inflammation, metabolic regulation, and autoimmunity, all of which are pathways linked to, and likely involved in, T1 and T2 diabetes pathogenesis. Several new proteins were differentially upregulated in prediabetic, T1D, and T2D pancreas. The results identify proteins that could serve as novel prognostic, diagnostic, and therapeutic tools to preserve functional islet mass in Type 1 Diabetes.