The Effect of Cholesterol on the Activation of TGF-β/Smad3C Signaling Pathway in Hepatic Stellate Cells and its role in the Progression of Liver Fibrogenesis

Document Type : Original Article (s)

10.22122/jims.v39i619.13838

Abstract

Background: Hepatic fibrosis is often attributed to activation of hepatic stellate cells (HSCs) and excessive scar formation in the liver. Because these cells overproduce extracellular matrix, the advanced stages of the disease often lead to liver cirrhosis and hepatocellular carcinoma. In this study, the role of cholesterol in the activation of hepatic stellate cells was investigated.
Methods: Cells were cultured in Dulbecco's modification of Eagle’s medium (DMEM) with 10% Fetal Bovine Serum (FBS), and treated with 25, 50, 75, and 100 μM cholesterol concentrations for 24 hours. Then, gene expression transforming growth factor beta (TGF-β) and collagen1α, as well as Smad3C protein level were measured to assess liver fibrosis.
Findings: The expression of TGF-β and collagen1α genes increased significantly compared to the control group at 75 and 100 μM cholesterol concentrations. In addition, Smad3C protein level increased significantly compared to the control group after 4 hours of cell treatment with a concentration of 100 μM cholesterol.
Conclusion: Cholesterol increases the major proteins involved in the production of extracellular matrix, including collagen1α, by increasing the level of the Smad3C protein and activating the TGF-β signaling pathway. As a result, cholesterol can lead to the development of liver fibrosis.

Keywords

References

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Journal of Isfahan Medical School
Volume 39, Issue 619
2021
Pages 212-218

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History

  • Receive Date: 01 April 2022
  • Accept Date: 01 April 2022

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