Galectin-3 in Liver Fibrosis

Galectin-3 在肝纤维化中的作用

• 批准号: 8623129
• 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
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8623129
• 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 therapeutics; prevent; response; stellate cell

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-2 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（申请人提供）：肝星状细胞（HSC）在肝纤维形成过程中发挥着至关重要的作用。肝细胞对凋亡小体的吞噬作用可诱导 HSC 活化，并上调前胶原 α 1(I) 和 TGF-2 的表达。此外，最近的数据表明 HSC 表现为抗原呈递细胞 (APC)。然而，它们在纤维发生过程中肝脏免疫反应调节中的作用尚不清楚。 Galectin-3 (Gal3) 是 2-半乳糖苷结合凝集素家族的成员，已知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 缺陷的 HSC 表现出吞噬活性降低和促纤维化活性降低，并且 Gal3-/- 小鼠的纤维化减少。因此，我们的假设是Gal3通过调节HSC的吞噬作用和抗原呈递以及随后的免疫反应在肝纤维化中发挥作用。为了检验这一假设，我们的具体目标是1）研究Gal3调节吞噬作用的机制，2）Gal3在肝纤维化过程中免疫反应调节中的作用，3）研究Gal3对促纤维发生和免疫调节的体内作用。此外，我们将在体内纤维化模型中使用Gal3抑制剂修饰的柑橘果胶（MCP）来评估其抗纤维化活性。这些研究可能会导致开发旨在逆转或预防肝纤维化的新治疗方法。