Using proteomics to elucidate pathogenesis and establish new diagnostic or treatment evaluation methods in refractory gastrointestinal diseases

利用蛋白质组学阐明难治性胃肠道疾病的发病机制并建立新的诊断或治疗评估方法

• 批准号: 23249043
• 负责人: TSUBOUCHI Hirohito
• 金额: $ 30.62万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23249043/
• 关键词: プロテオミクス; C型慢性肝炎; HCV; AIM; 補体C4断片; ヒト好中球ペプチド; 炎症性腸疾患; NAFLD; 膵炎; 肝細胞癌; 非アルコール性脂肪肝炎; 膵癌; 自己免疫性膵炎; 潰瘍性大腸炎; クローン病

We identified several serum proteins present at high levels in patients with liver disease or inflammatory bowel disease, including complement component C4 fragment (C4-F), kininogen fragment (Kini-F), apoptosis inhibitor (AIM), and human neutrophil peptide (HNP)-1. Serum C4-F and Kini-F are potentially biomakers for antiviral effects in patients with chronic hepatitis C or diagnosis of nonalcoholic fatty liver disease (NAFLD), respectively. In patients with chronic liver disease, serum AIM levels were associated with liver fibrosis. AIM also appeared to contribute to the pathogenesis of NAFLD. Furthermore, HNP-1 worsened pathological condition in the mouse model of NAFLD and alcoholic liver disease, in addition to ulcerative colitis. Thus, proteomics is a useful tool for identifying proteins that might serve as candidate biomarkers in refractory gastrointestinal diseases, and the identified proteins may be involve in the pathological conditions associated with those diseases.

我们鉴定了几种在肝病或炎症性肠病患者中高水平存在的血清蛋白，包括补体成分C4片段（C4-F）、激肽原片段（Kini-F）、凋亡抑制剂（AIM）和人中性粒细胞肽（HNP）-1。血清C4-F和Kini-F分别是慢性丙型肝炎患者或非酒精性脂肪性肝病（NAFLD）诊断患者抗病毒作用的潜在生物标志物。在慢性肝病患者中，血清AIM水平与肝纤维化相关。AIM似乎也有助于NAFLD的发病机制。此外，除了溃疡性结肠炎之外，HNP-1还使NAFLD和酒精性肝病小鼠模型的病理状况恶化。因此，蛋白质组学是一种有用的工具，用于鉴定可能作为难治性胃肠道疾病的候选生物标志物的蛋白质，并且所鉴定的蛋白质可能参与与这些疾病相关的病理条件。

项目成果

C型肝炎ウイルス持続感染者の病態と補体C3，C4との関連の検討

丙型肝炎病毒持续感染者病理状况与补体C3、C4关系的探讨

• 发表时间: 2012
• 作者: 馬渡誠一;他
• 通讯作者: 他

ヒト好中球ペプチド-1はNASH動物モデルの肝線維化を促進する

人中性粒细胞肽-1促进NASH动物模型肝纤维化

• 发表时间: 2011
• 作者: 宇都浩文;指宿りえ;坪内博仁
• 通讯作者: 坪内博仁

Hepatic fibrosis and apoptosis induced by ethanol administration are exacerbated in human neutrophil peptide-1 transgenic mice

人中性粒细胞肽-1转基因小鼠中乙醇诱导的肝纤维化和细胞凋亡加剧

• 发表时间: 2014
• 作者: Ibusuki R;Uto H;Kozono M;Oda K;Ohshige A;Kumagai K;Mawatari S;Tamai T;Moriuchi A;Oketani M;Ido A;Tsubouchi H
• 通讯作者: Tsubouchi H

Long-term administration of sorafenib and initial dosage per body weight are associated with overall survival in patients with unresectable advanced hepatocellular carcinoma

索拉非尼的长期给药和单位体重的初始剂量与不可切除的晚期肝细胞癌患者的总生存期相关

• 发表时间: 2011
• 作者: Hiramine Y;Uto H;et al
• 通讯作者: et al

Difference in serum complement component C4a levels between hepatitis C virus carriers with persistently normal alanine aminotransferase levels or chronic hepatitis C.

• DOI: 10.3892/mmr.2012.924
• 发表时间: 2012-08
• 期刊: Molecular medicine reports
• 影响因子: 3.4
• 作者: Imakiire K;Uto H;Sato Y;Sasaki F;Mawatari S;Ido A;Shimoda K;Hayashi K;Stuver SO;Ito Y;Okanoue T;Tsubouchi H
• 通讯作者: Tsubouchi H