Intestinal proteome changes during infant necrotizing enterocolitis

Intestinal proteome changes during infant necrotizing enterocolitis
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DOI:
10.1038/pr.2012.182
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发表时间:
2013-03-01
期刊:
影响因子:
3.6
通讯作者:
Sangild, Per Torp
Sangild, Per Torp
中科院分区:
医学3区
文献类型:
--
作者:
Jiang, Pingping;Smith, Birgitte;Sangild, Per Torp

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背景:坏死性小肠结肠炎(NEC)患者肠道和结肠蛋白质组的变化可能有助于确定疾病的病理特征,寻找新的生物标志物和治疗靶点。方法:采用基于凝胶的蛋白质组学方法,比较同一患者中NEC感染的肠和结肠组织中的蛋白质和邻近、接近正常的组织中的蛋白质。结果:用免疫印迹和免疫组织化学方法对部分蛋白质组数据和组织学定位进行交叉验证。结果:30个蛋白质在坏死区和活体小肠组织中差异表达,23个蛋白质在结肠组织中差异表达。在小肠和结肠中有五种蛋白质受到类似的影响:组胺受体(HRs)、肌动蛋白、球蛋白、免疫球蛋白和抗胰蛋白酶。两种热休克蛋白(HSPs)在小肠中受到影响。此外,参与抗氧化、血管生成、细胞骨架形成和新陈代谢的蛋白质也受到影响。最后,NEC的分泌蛋白如抗胰蛋白酶、脂肪酸结合蛋白5和结合珠蛋白在受NEC影响的组织和生命组织中存在差异。结论:NEC进展影响小肠和结肠的不同途径。热休克蛋白可能发挥重要作用,特别是在小肠。已鉴定的分泌蛋白应作为NEC在不同肠道区域进展的可能循环标志物进行研究。
BACKGROUND: Changes in the intestinal and colonic proteome in patients with necrotizing enterocolitis (NEC) may help to characterize the disease pathology and identify new biomarkers and treatment targets for NEC.METHODS: Using gel-based proteomics, proteins in NEC-affected intestinal and colonic sections were compared with those in adjacent, near-normal tissue sections within the same patients. Western blot and immunohistochemistry were applied to crossvalidate proteomic data and histological location of some selected proteins.RESULTS: Thirty proteins were identified with differential expression between necrotic and vital small-intestine sections and 23 proteins were identified for colon sections. Five proteins were similarly affected in the small intestine and colon: histamine receptors (HRs), actins, globins, immunoglobulin, and antitrypsin. Two heat shock proteins (HSPs) were affected in the small intestine. Furthermore, proteins involved in antioxidation, angiogenesis, cytoskeleton formation, and metabolism were affected. Finally, secretory proteins such as antitrypsin, fatty-acid binding protein 5, and haptoglobin differed between NEC-affected and vital tissues.CONCLUSION: NEC progression affects different pathways in the small intestine and colon. HSPs may play an important role, especially in the small intestine. The identified secretory proteins should be investigated as possible circulating markers of NEC progression in different gut regions.