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.

Public Health Relevance

Hepatic stellate cells produce extra collagen upon phagocytosing injured hepatocytes which leads to fibrosis and cirrhosis, and act as antigen presenting cells participating hepatic immune regulation. In the current study, we propose that galectin-3, an important immune regulator, plays a role in live fibrosis by mediating stellate cell phagocytosis and the subsequent immune reactions. The findings obtained from this project may lead to the development of new therapeutic strategies in the future.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Podskalny, Judith M,
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University of California Davis
Internal Medicine/Medicine
Schools of Medicine
United States
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