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Increased, Activation and Recruitment of Hepatic macrophages (Kupffer Cells) leads to Up Regulation, TGFbeta1 expression
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Following activation Kupffer cells (KCs) become the main source for TGF-β1, the most potent profibrogenic cytokine, as well as a major source for inflammatory mediators and for reactive oxygen species (ROS).
Expressed TNF-α (Tumor Necrosis Factor -alpha), TRAIL (TNF-related apoptosis-inducing ligand), and FasL (Fas Ligand) are pro-inflammatory active and also capable of inducing death receptor-mediated apoptosis in hepatocytes.
Activated KCs are an important source of ROS like superoxide (generated by NADPH oxidase (NOX). KCs express TNF-α, IL-1 (Interleukin-1) and MCP-1 (monocyte-chemoattractant protein-1), all being mitogens and chemoattractants for HSCs and induce the expression of platelet-derived growth factor (PDGF) receptors on hepatic stellate cells (HSCs) which further enhances HSCs proliferation
Evidence Collection Strategy
Evidence Supporting this KER
Uncertainties and Inconsistencies
there are no inconsistencies
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
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