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Updated: Aug 6, 2025
Seven Steps to Stellate Cells
Published on: May 10, 2011
CD73 Blockade Alleviated Hepatic Fibrosis via Inhibiting Hepatic Stellate Cells Proliferation and Activation
Lan Yang1, Zhao-Wei Gao1, Xia-Nan Wu1
1Department of Clinical Laboratory, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi Province, China.
Background:
Liver fibrosis is associated with the activation of hepatic stellate cells (HSCs). Inhibition of HSCs activation is a strategy for alleviating hepatic fibrogenesis. CD73 is involved in liver disease development, while the mechanism remains unclear.
Objective:
This study aimed to investigate the effect of CD73 targeting inhibition on liver fibrosis.
Methods:
Intraperitoneal injection of CCl4 was used to induce liver fibrosis in mice models. Adenosine 5'-(α, β-methylene) diphosphate sodium salt (APCP) was used for CD73 blockade. The siRNA was used to induce CD73 knockdown in HSCs. LX2 and HSC-T6 were used to investigate the role of CD73 in HSCs activation in vitro.
Results:
The results showed that APCP treatment could alleviate hepatic fibrosis. In fibrotic liver tissues, CD73 exhibited a positive correlation with markers of HSCs activation. Furthermore, APCP treatment and CD73 knockdown could inhibit HSCs (LX2 and HSC-T6) activation and proliferation. By using RNA sequencing of liver tissues from control, CCl4-mice, and APCP-treated mice, 851 genes that were significantly changed in CCl4 mice (vs. control) were reversed by APCP treatment. These genes were mainly enriched in cell division-associated biological processes. Moreover, we found that CD73 might be associated with autophagy in HSCs. In fibrotic liver tissues and HSCs, ATG5 and Beclin1 expression could be downregulated by CD73 knockdown and APCP treatment.
Conclusion:
This study demonstrated the effects and mechanism of CD73 in HSCs activation and proliferation, which presents the therapeutical potential of CD73 blockage for liver fibrosis.
Insights
Targeting CD73 (Cluster of Differentiation 73) with APCP (adenosine 5
Area of Science:
- Hepatology and Immunology
- Molecular Biology
- Drug Discovery
Background:
- Liver fibrosis involves hepatic stellate cell (HSC) activation, a key target for antifibrotic strategies.
- The precise role of CD73 in liver disease pathogenesis and HSC activation remains incompletely understood.
Purpose of the Study:
- To elucidate the functional impact of CD73 inhibition on liver fibrosis progression.
- To investigate the underlying molecular mechanisms by which CD73 influences HSC activation and proliferation.
Main Methods:
- Establishment of a carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis.
- Pharmacological blockade of CD73 using Adenosine 5'-(α, β-methylene) diphosphate sodium salt (APCP).
- In vitro studies utilizing LX2 and HSC-T6 cell lines with CD73 knockdown via siRNA.
Main Results:
- APCP treatment significantly ameliorated liver fibrosis and reduced HSC activation markers.
- CD73 blockade and knockdown inhibited HSC proliferation and activation.
- RNA sequencing revealed APCP reversed CCl4-induced gene expression changes, particularly in cell division pathways.
- CD73 inhibition downregulated autophagy-related proteins ATG5 and Beclin1 in fibrotic liver tissues and HSCs.
Conclusions:
- CD73 plays a critical role in HSC activation and proliferation, contributing to liver fibrosis.
- Targeting CD73 demonstrates therapeutic potential for managing liver fibrosis.
