Elevated ER stress exacerbates dextran sulfate sodium-induced colitis in PRDX4-knockout mice

Area of Science:

• Cell Biology
• Immunology
• Gastroenterology

Background:

• Peroxiredoxin 4 (PRDX4) is a secretory protein retained in the endoplasmic reticulum (ER), highly expressed in colonic tissue.
• PRDX4 plays a role in cellular defense mechanisms, including antioxidant activity and ER stress response.

Purpose of the Study:

• To investigate the role of PRDX4 in the development of intestinal inflammation.
• To evaluate the impact of PRDX4 deficiency on dextran sulfate sodium (DSS)-induced colitis in a mouse model.

Main Methods:

• Utilized male PRDX4-knockout (PRDX4^-/y) and wild-type (WT) C57BL/6 mice.
• Induced acute colitis using DSS (2.5% in drinking water).
• Performed histological and biochemical analyses on colonic tissues, including disease activity index (DAI) scoring, myeloperoxidase levels, and inflammatory cytokine mRNA expression (TNF-α, IFN-γ).

Main Results:

• PRDX4^-/y mice exhibited significantly higher DAI scores, body weight loss, and colon shortening compared to WT mice.
• Increased myeloperoxidase levels and elevated mRNA expression of TNF-α and IFN-γ were observed in PRDX4^-/y mice.
• PRDX4 deficiency led to increased CHOP and activated caspase 3 levels, indicating heightened ER stress and apoptosis, along with greater ER expansion.

Conclusions:

• Lack of PRDX4 exacerbates DSS-induced colonic mucosal damage.
• PRDX4 deficiency results in greater oxidative damage and ER stress in response to DSS.
• PRDX4 may serve as a novel therapeutic target for managing intestinal inflammation.