Galectin-3 in Liver Fibrosis

Galectin-3 在肝纤维化中的作用

基本信息

批准号：
9062424
负责人：
Xiaosong Joy Jiang
金额：
$ 13.14万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-01 至 2017-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9062424
关键词：
Address Antigen Presentation Antigen-Presenting Cells Apoptotic Binding Biological Response Modifiers CD4 Positive T Lymphocytes Cells Cirrhosis Citrus Coculture Techniques Collagen Collagen Type I Data Development Event Extracellular Matrix Family Fibrosis Future Galactosides Galectin 2 Galectin 3 Hepatic Hepatic Fibrogenesis Hepatic Stellate Cell Hepatocyte Immune Immune response Inflammatory Integrins Lead Lectin Life Ligation Liver Fibrosis Lymphocyte Subset Mediating Mediator of activation protein Modality Modeling Mus Pectins Peritoneal Macrophages Phagocytosis Play Process Procollagen Reaction Regulation Role Signal Pathway Testing Transforming Growth Factors Up-Regulation bile duct cytokine fibrogenesis immunoregulation in vivo inhibitor/antagonist injured member novel therapeutic intervention novel therapeutics prevent response stellate cell

项目摘要

DESCRIPTION (provided by applicant): Hepatic stellate cells (HSC) play a crucial role during liver fibrogenesis. Phagocytosis of apoptotic bodies from hepatocytes induces HSC activation with upregulation of procollagen alpha 1(I) and TGF-ß expression. In addition, recent data indicate that HSC behave as antigen presenting cells (APC). However, their role in the regulation of hepatic immune responses during fibrogenesis is not well understood. Galectin-3 (Gal3), a member of 2-galactoside-binding lectin family is known to regulate cell phagocytosis and also is an important immune regulator. According to our preliminary data Gal3 is an important mediator of liver fibrosis as Gal3 deficient HSC displayed decreased phagocytic activity and diminished profibrogenic activity and Gal3-/- mice developed decreased fibrosis. Therefore, our hypothesis is that Gal3 plays a role in liver fibrosis by regulating HSC phagocytosis and antigen presentation, and the subsequent immune responses. To test this hypothesis, our specific aims are 1) to study the mechanisms by which Gal3 regulates phagocytosis, 2) the role of Gal3 in the regulation of immune responses during liver fibrosis, and 3) the in vivo effects of Gal3 on profibrogenesis and immunoregulation will be studied. In addition, we will use the Gal3 inhibitor modified citrus pectin (MCP) in the in vivo fibrosis model to assess its antifibrogenic activity. These studies may lead to the development of new therapeutic modalities aimed at reversing or preventing liver fibrosis.

描述（由适用提供）：肝星状细胞（HSC）在肝纤维发生过程中起着至关重要的作用。肝细胞中凋亡人体的吞噬作用会影响HSC激活，而Procollagen alpha 1（i）和TGF-ß表达的上调。另外，最近的数据表明HSC作为抗原呈递细胞（APC）的行为。但是，它们在纤维化过程中肝免疫反应调节中的作用尚不很好。 Galectin-3（Gal3）是2-半乳糖苷结合授课家族的成员，可调节细胞吞噬作用，也是重要的免疫调节剂。根据我们的初步数据，GAL3是肝纤维化的重要介质，因为GAL3缺乏HSC显示出降低的吞噬活性和纤维化活性的降低，而GAL3 - / - 小鼠发出的纤维化降低了。因此，我们的假设是GAL3通过调节HSC吞噬作用和抗原表现以及随后的免疫调查中的作用在肝纤维化中起作用。为了检验这一假设，我们的具体目的是1）研究GAL3调节吞噬作用的机制，2）GAL3在肝纤维化过程中GAL3在调节免疫调查中的作用，以及3）GAL3对纤维化和免疫调查的体内影响将是研究的。此外，我们将在体内纤维化模型中使用GAL3抑制剂改性果果蛋白（MCP）来评估其抗纤维化活性。这些研究可能导致旨在逆转或预防肝纤维化的新治疗方式的发展。