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Syndecan-1 in liver pathophysiology.

Andrea Reszegi1, Péter Tátrai2, Eszter Regős3

  • 1Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.

American Journal of Physiology. Cell Physiology
|June 15, 2022
PubMed
Summary

Syndecan-1 (SDC-1), a key proteoglycan, plays a crucial role in liver diseases like cirrhosis and cancer. Its elevated levels indicate poor prognosis and it impacts viral uptake and disease progression.

Keywords:
extracellular matrixfibrosisliver cancerproteoglycansyndecan-1

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Hepatology

Background:

  • Syndecan-1 (SDC-1) is a cell surface and extracellular matrix proteoglycan regulating diverse physiological and pathological processes.
  • It is the major proteoglycan in the liver, expressed by hepatocytes and cholangiocytes, with elevated levels characteristic of liver diseases.

Purpose of the Study:

  • To investigate the role of Syndecan-1 in liver pathologies, including fibrogenesis, hepatocarcinogenesis, and viral infections.
  • To explore the clinical significance of serum levels of the shed extracellular domain of Syndecan-1.

Main Methods:

  • Analysis of Syndecan-1 expression in liver disease models.
  • In vivo experiments to assess Syndecan-1's protective effects against fibrogenesis and hepatocarcinogenesis.
  • Evaluation of Syndecan-1's role in lipid metabolism, ribosomal biogenesis, and viral uptake (HCV, SARS-CoV-2).

Main Results:

  • Highest Syndecan-1 expression observed in liver cirrhosis and hepatocellular carcinoma (HCC).
  • Hepatitis C virus (HCV)-infected livers show significantly increased Syndecan-1 production.
  • In vivo studies demonstrated Syndecan-1 protects against early fibrogenesis and hepatocarcinogenesis by clearing TGFβ1 and THBS1, interfering with signaling pathways, and inducing cell cycle blockade.

Conclusions:

  • Elevated serum levels of shed Syndecan-1 correlate with poor prognosis in cirrhosis and cancer.
  • Syndecan-1 hinders lipid metabolism and ribosomal biogenesis in cancer models.
  • Syndecan-1 is a central player in liver pathologies, influencing fibrogenesis, cancer development, and viral infections.