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Updated: May 9, 2026
Seven Steps to Stellate Cells
Published on: May 10, 2011
[Role of macrophage migration inhibitory factor in hepatic stellate cells activation]
Yong-Jun Zhu1, Xiao-Lin Hu, Ruo-Ting Men
1Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.
Objective:
To investigate the role of macrophage migration inhibitory factor (MIF) in activation of primary hepatic stellate cells (HSC), and to explore the blocking effect of specific antisense oligonucleotides (ASONs) targeting MIF on the activation of primary HSCs.
Methods:
Rat primary HSC were isolated from SD rats by in situ perfusion of collagenase and pronase and single-step Nycodenz density gradient centrifugation, and then cultured and activated. The expression of alpha-smooth muscle actin (alpha-SMA), the marker of HSC activation, was assessed by RT-PCR and immunocytochemistry (ICC). The expression of MIF was detected by RT-PCR, enzyme-linked immuno sorbent assay (ELISA), immunofluorescence (IF) or ICC. Completely activated primary HSC were transfected with MIF-specific antisense oligonucleotide (MIF-ASONs), mis-sense oligonucleotides of MIF, or blank liposome (negative-control).
Results:
Quiescent HSC expressed very low level of MIF, while MIF gene and protein expression increased significantly during the process of HSC activation. Positive correlation was found between the expression of alpha-SMA and MIF (r = 0.944, P < 0.01). Compared with the control, activated primary Gen HSC transfected with MIF-ASONs showed lower MIF and alpha-SMA expressions at gene and protein profiles (P < 0.05).
Conclusion:
The expression of MIF was up-regulated in the process of HSC activation. Activation in culture of primarily isolated rat HSC could be inhibited by MIF-ASONs, suggesting at least in part that, MIF might be a novel and important factor involved in HSC activation and hepatic fibrosis.
Insights
Macrophage migration inhibitory factor (MIF) is upregulated during hepatic stellate cell (HSC) activation. Specific antisense oligonucleotides targeting MIF effectively inhibited HSC activation, suggesting MIF
Area of Science:
- Hepatology
- Cell Biology
- Molecular Medicine
Background:
- Hepatic stellate cells (HSCs) play a critical role in liver fibrosis.
- Activation of HSCs is a key event in the pathogenesis of liver fibrosis.
- Understanding the molecular mechanisms regulating HSC activation is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of macrophage migration inhibitory factor (MIF) in the activation of primary HSCs.
- To explore the potential of MIF-specific antisense oligonucleotides (ASONs) to block HSC activation.
Main Methods:
- Primary rat HSCs were isolated and cultured.
- HSC activation was assessed by alpha-smooth muscle actin (alpha-SMA) expression.
- MIF expression was measured using RT-PCR, ELISA, and immunocytochemistry.
- Activated HSCs were transfected with MIF-specific ASONs, control ASONs, or liposomes.
Main Results:
- MIF expression was significantly upregulated during HSC activation.
- A strong positive correlation was observed between alpha-SMA and MIF expression.
- MIF-ASONs treatment significantly reduced MIF and alpha-SMA expression in activated HSCs.
Conclusions:
- MIF expression is upregulated during HSC activation.
- MIF plays a significant role in HSC activation and potentially hepatic fibrosis.
- MIF-specific ASONs demonstrate potential as a therapeutic strategy to inhibit HSC activation.
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