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Vitamin D supplementation ameliorates ductular reaction, liver inflammation and fibrosis in mice by upregulating TXNIP in ductular cells

  • 0College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
Nature Communications +

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May 13, 2025

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May 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Vitamin D deficiency worsens liver disease. Active vitamin D (1,25(OH)2D3) protects against liver damage by upregulating TXNIP in bile duct cells, revealing a new therapeutic target for liver diseases.

Area Of Science

  • Hepatology
  • Endocrinology
  • Molecular Biology

Background

  • Ductular reaction is a hallmark of liver disease progression, yet lacks targeted therapies.
  • Vitamin D deficiency is prevalent in chronic liver diseases, but its role in disease mechanisms is not fully understood.

Purpose Of The Study

  • To investigate the role of vitamin D and its target gene TXNIP in regulating ductular reaction and liver disease progression.
  • To elucidate the underlying mechanisms of vitamin D's protective effects in liver disease.

Main Methods

  • Correlation analysis of vitamin D levels and ductular reaction in patients.
  • Mouse models of liver injury (DDC-induced) with genetic manipulation of TXNIP in cholangiocytes.
  • Assessment of liver inflammation, fibrosis, cell proliferation, death, and cytokine secretion.

Main Results

  • Vitamin D levels negatively correlate with ductular reaction severity in chronic liver disease patients.
  • Active vitamin D (1,25(OH)2D3) reduced DDC-induced ductular reaction, inflammation, and fibrosis in mice.
  • TXNIP upregulation in ductular cells by vitamin D is crucial; its deficiency exacerbates liver injury by promoting cholangiocyte proliferation and increasing pro-inflammatory cytokine secretion.

Conclusions

  • The vitamin D/TXNIP axis plays a critical role in ameliorating liver disease progression.
  • Targeting the vitamin D/TXNIP pathway offers a potential therapeutic strategy for ductular reaction and associated liver diseases.