Origin of myofibroblasts in liver fibrosis

David A Brenner1, Tatiana Kisseleva1, David Scholten1

  • 1University of California, San Diego, School of Medicine, San Diego, CA, USA.

Insights

Liver fibrosis, a hallmark of chronic liver disease, involves myofibroblasts producing scar tissue. Their precise origin in liver fibrosis remains an active area of research and investigation.

Area of Science:

  • Hepatology
  • Cell Biology
  • Fibrosis Research

Background:

  • Chronic liver diseases lead to progressive liver fibrosis.
  • Myofibroblasts are key cells in producing the fibrous scar tissue (extracellular matrix, including type I collagen) characteristic of liver fibrosis.
  • Myofibroblasts are present early in liver injury, but their origin in fibrosis is not fully understood.

Purpose of the Study:

  • To review the current understanding of the origin of myofibroblasts in liver fibrosis.
  • To explore potential sources of myofibroblasts, including endogenous mesenchymal cells, bone marrow recruitment, and cell transformation.
  • To consider if myofibroblast origins differ among various chronic liver disease etiologies.

Main Methods:

  • Literature review of experimental and clinical studies on liver fibrosis.
  • Analysis of research investigating myofibroblast origins in different liver disease models.
  • Synthesis of current knowledge on hepatic stellate cell activation, bone marrow-derived cell contribution, and epithelial-to-myofibroblast transition.

Main Results:

  • Myofibroblasts are central to scar formation in liver fibrosis.
  • Several potential origins for myofibroblasts exist, including hepatic stellate cells and potentially other cell types.
  • The specific origin of myofibroblasts may vary depending on the underlying cause of liver disease.

Conclusions:

  • The origin of myofibroblasts in liver fibrosis is complex and likely multifactorial.
  • Understanding myofibroblast origins is crucial for developing targeted therapies for liver fibrosis.
  • Further research is needed to elucidate the distinct pathways contributing to myofibroblast populations in diverse chronic liver diseases.

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