Publication Date
5-2015
Date of Final Oral Examination (Defense)
3-16-2015
Type of Culminating Activity
Thesis
Degree Title
Master of Science in Biology
Department
Biology
Supervisory Committee Chair
Kristen A. Mitchell, Ph.D.
Supervisory Committee Member
Kenneth A. Cornell, Ph.D.
Supervisory Committee Member
Julia Thom Oxford, Ph.D.
Abstract
Liver regeneration is a complex process that requires the coordinated expression of cytokines and growth factors. One well-studied model of liver regeneration is partial hepatectomy (PH), in which removal of 70% of the liver initiates compensatory hepatocyte proliferation. PH-induced liver regeneration requires the activation of resident macrophages (Kupffer cells), which produce cytokines that drive hepatocyte proliferation. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is known to activate macrophages and recruit monocytes during tissue injury. The goal of this study was to determine how MCP-1 contributes to macrophage activation during liver regeneration. Results indicate that hepatic and plasma MCP-1 levels increased within 12 hr after PH and correlated with hepatic recruitment of cells expressing the MCP-1 receptor, CCR2. Nevertheless, hepatocyte proliferation was comparable in MCP-1 knockout and wild-type mice, as was the expression of Kupffer cell-derived cytokines. Furthermore, hepatic recruitment of CCR2+ cells was similar in MCP-1 knockout and wild-type mice, which suggests that other chemokines may efficiently recruit CCR2+ cells in the absence of MCP-1. CCR2 appears to be required for optimal regeneration, as CCR2 knockout mice had levels of hepatocyte proliferation that were 50% lower than wild-type mice 36 hr after PH. We conclude that MCP-1 is not required for macrophage activation during PH-induced liver regeneration. Future studies should instead focus on mechanisms by which CCR2 signaling events and the hepatic recruitment of CCR2-expressing cells facilitates hepatocyte proliferation during liver regeneration.
Recommended Citation
Wyler, Stephanie, "Role of Monocyte Chemoattractant Protein-1 During Liver Regeneration" (2015). Boise State University Theses and Dissertations. 942.
https://scholarworks.boisestate.edu/td/942