Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and liver fibrosis: A review

Keywan Mortezaee1

  • 1Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Insights

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) drive liver fibrosis by activating hepatic stellate cells and Kupffer cells. NOX1, 2, and 4 are key inducers of liver fibrosis through multiple cellular pathways.

Area of Science:

  • Hepatology
  • Cell Biology
  • Biochemistry

Background:

  • Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are critical sources of reactive oxygen species in liver cells.
  • Hepatic stellate cells (HSCs) and Kupffer cells (KCs) are the primary liver cells expressing NOX enzymes.

Purpose of the Study:

  • To investigate the role of NOX subtypes in liver fibrosis.
  • To elucidate the cellular mechanisms by which NOXs contribute to fibrogenesis.

Main Methods:

  • The study focused on the expression and function of NOX1, NOX2, and NOX4 in HSCs and KCs.
  • Analysis of NOX-mediated pathways involved in HSC activation, proliferation, migration, hepatocyte apoptosis, and inflammation.

Main Results:

  • KCs exclusively produce NOX2, whereas HSCs express NOX1, NOX2, and NOX4.
  • All investigated NOX subtypes are implicated in promoting liver fibrogenesis.
  • NOX activation contributes to HSC activation, proliferation, survival, and migration.
  • NOX signaling enhances hepatocyte apoptosis and stimulates fibrogenic mediators.
  • NOX activity mediates inflammatory cascades within KCs and HSCs.

Conclusions:

  • HSCs and KCs are central to NOX production in the context of liver fibrosis.
  • NOX1, NOX2, and NOX4 are significant contributors to liver fibrogenesis.
  • NOX activation exacerbates liver fibrosis by promoting hepatocyte apoptosis, HSC activation, and KC-driven inflammation.

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