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Hepatic stellate cell as a Mac-2-binding protein-producing cell in patients with liver fibrosis

Dolgormaa Gantumur1, Norifumi Harimoto1,2, Ryo Muranushi1

  • 1Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, Maebashi, Japan.

Hepatology Research : the Official Journal of the Japan Society of Hepatology
|April 20, 2021
PubMed
Abstract

Insights

Mac-2 binding protein (M2BP) mRNA is transcribed in hepatic stellate cells (HSCs) in fibrotic livers. While HSCs may produce M2BP, Kupffer cells express the M2BP protein, suggesting a transfer mechanism.

Area of Science:

  • Hepatology
  • Biochemistry
  • Immunology

Background:

  • Mac-2 binding protein (M2BP) glycosylated isomer (M2BPGi) is a serum biomarker for liver fibrosis.
  • The cellular origin of M2BP in fibrotic liver tissue remains to be fully elucidated.
  • Hepatocytes and hepatic stellate cells (HSCs) are potential sources of M2BP.

Purpose of the Study:

  • To identify the cellular origin of M2BP in fibrotic liver tissue.
  • To investigate the relationship between M2BP mRNA expression and established fibrosis markers.

Main Methods:

  • In situ hybridization and immunohistochemistry were used to detect M2BP mRNA and protein in liver specimens from 15 cancer patients with fibrosis.
  • Fluorescent in situ hybridization and multicolor fluorescent immunohistochemistry were employed to assess co-localization of M2BP, HSC markers (αSMA), and Kupffer cell markers (CD68).
  • Statistical analysis (Kruskal-Wallis test) examined correlations between M2BP mRNA expression and serum fibrosis markers.

Main Results:

  • M2BP mRNA was detected in spindle-shaped cells in fibrous septa and perisinusoidal areas, co-localizing with HSC markers (αSMA mRNA).
  • At the protein level, M2BP was found in Kupffer cells.
  • M2BP mRNA expression positively correlated with serum M2BPGi levels and other fibrosis markers (APRI, FIB-4, hyaluronic acid, ICG retention).

Conclusions:

  • M2BP mRNA transcription in fibrotic liver primarily occurs in HSCs.
  • The protein localization of M2BP in Kupffer cells suggests HSCs may produce and transfer M2BP to Kupffer cells and serum.
  • These findings offer insights into the pathogenesis of liver fibrosis and the role of M2BP.
Keywords:
M2BPM2BPGihepatic stellate cellliver fibrosis

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