Related Experiment Video
Updated: Apr 28, 2026
06:40
Seven Steps to Stellate Cells
Published on: May 10, 2011
33.7K
Anaphylatoxin C5a modulates hepatic stellate cell migration.
Dola Das1, Mark A Barnes2, Laura E Nagy3
1Center for Liver Disease Research, Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Fibrogenesis & Tissue Repair
|June 12, 2014
Summary
Complement component C5a (in brackets, C5a) drives liver fibrosis by enhancing the migration of hepatic stellate cells (in brackets, HSC). This suggests C5a and its receptors are potential therapeutic targets for liver fibrosis treatment.
Area of Science:
- Immunology
- Hepatology
- Complement System Biology
Background:
- The complement system, particularly C5a and its receptor C5aR, plays a role in liver immunity and fibrosis.
- The precise molecular mechanisms linking complement activation to liver fibrosis remain unclear.
- Hepatic stellate cell (HSC) activation and migration are key drivers of liver fibrosis.
Purpose of the Study:
- To investigate the role of C5a in regulating HSC activation and migration.
- To elucidate the molecular mechanisms by which C5a influences liver fibrosis.
Main Methods:
- Primary mouse HSC cultures were used to assess alpha smooth muscle actin (α-SMA) and collagen 1A (Col1A1) mRNA expression.
- C5a receptor (C5aR) expression was analyzed by RT-PCR, immunocytochemistry, and flow cytometry.
- HSC migration assays (wound healing and Boyden chamber) were performed with and without C5a stimulation.
- The effect of a monocyte chemoattractant protein-1 (MCP-1) receptor antagonist on C5a-induced migration was evaluated.
Main Results:
- HSC activation in culture led to increased C5aR mRNA expression.
- C5a stimulation did not affect HSC activation markers (α-SMA, Col1A1).
- C5a significantly enhanced HSC migration, comparable to platelet-derived growth factor (PDGF).
- C5a also stimulated MCP-1 expression, and its migratory effect was partially dependent on MCP-1 signaling.
Conclusions:
- C5a directly regulates HSC migration, independent of HSC activation.
- This study reveals a novel mechanism involving complement-mediated HSC migration in hepatic fibrosis.
- C5a and its receptors represent potential therapeutic targets for liver fibrosis.
Related Concept Videos
01:24Cirrhosis II: Pathophysiology
41
Cirrhosis is a progressive chronic liver injury caused by prolonged inflammation, excessive fibrotic remodeling, and impaired regeneration. Over time, repeated hepatic insults disrupt the liver’s architecture and function, leading to reduced blood flow, impaired bile drainage, and diminished metabolic capacity.Pathophysiology of cirrhosisCirrhosis arises from three main responses to chronic liver damage: inflammation, immune activation, and hepatocyte death. These processes lead to...
41
01:24Liver Regeneration
4.1K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
4.1K
01:17Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
01:24T Cell Types and Functions
3.2K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.2K