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Updated: Mar 5, 2026

Analyzing Oxidative Stress in Murine Intestinal Organoids using Reactive Oxygen Species-Sensitive Fluorogenic Probe
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Analyzing Oxidative Stress in Murine Intestinal Organoids using Reactive Oxygen Species-Sensitive Fluorogenic Probe

Published on: September 17, 2021

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Protection against oxidative stress mediated by the Nrf2/Keap1 axis is impaired in Primary Biliary Cholangitis

Urszula Wasik1, Małgorzata Milkiewicz1, Agnieszka Kempinska-Podhorodecka1

  • 1Department of Medical Biology Laboratory, Pomeranian Medical University, Szczecin, Poland.

Scientific Reports
|March 24, 2017
PubMed

Insights

In primary biliary cholangitis (PBC), the Nrf2 pathway is impaired, reducing the body's defense against oxidative stress. This impairment is worse in patients with cirrhosis, indicating a role for the Nrf2/Keap1 system in PBC progression.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Cellular Stress Response

Background:

  • Oxidative stress is implicated in liver diseases like primary biliary cholangitis (PBC).
  • The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway is a key regulator of cellular defense against oxidative stress.
  • Nrf2 activity is modulated by Kelch-like ECH-associated protein1 (Keap1) and autophagy.

Purpose of the Study:

  • To investigate the role of the Nrf2/Keap1 axis in the context of oxidative stress in primary biliary cholangitis.
  • To assess the integrity of the Nrf2/Keap1 system and autophagy in PBC patients with and without cirrhosis.

Main Methods:

  • Analysis of liver specimens from PBC patients (with and without cirrhosis) and controls.
  • Molecular analyses including protein and gene expression of Nrf2, Keap1, p62, HO-1, GCLC, microRNA-132, and microRNA-34a.
  • Assessment of autophagy markers and Nrf2 pathway activation.

Main Results:

  • Nrf2 protein levels were elevated in PBC, but Nrf2 gene expression was reduced in cirrhotic PBC.
  • Nrf2 target genes (HO-1, GCLC) were reduced in PBC.
  • Elevated microRNA-132 and microRNA-34a levels were associated with reduced Nrf2 gene expression.
  • Keap1 and p62 protein levels were increased in PBC.
  • PBC showed reduced Nrf2 expression and impaired autophagy, with more severe impairments in cirrhotic cases.

Conclusions:

  • Primary biliary cholangitis is associated with impaired Nrf2/Keap1 system integrity and autophagy dysfunction.
  • These impairments contribute to reduced self-defense mechanisms against oxidative stress in PBC.
  • Cirrhosis exacerbates these molecular deficits in PBC patients.

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