Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin

Area of Science:

• Gastroenterology and Immunology
• Molecular Biology and Genetics

Background:

• Gastrointestinal diseases often involve chronic inflammation leading to tissue damage.
• Angiopoietin-like 4 (ANGPTL4) is linked to inflammation-associated diseases, but its role in colonic inflammation is unknown.

Purpose of the Study:

• To investigate the role of ANGPTL4 in regulating colonic inflammation.
• To determine if ANGPTL4 deficiency exacerbates or ameliorates inflammation-induced colonic damage.

Main Methods:

• Utilized ANGPTL4-deficient (ANGPTL4^-/-) and wild-type (ANGPTL4^+/+) mice challenged with dextran sulfate sodium (DSS) or stearic acid.
• Analyzed colonic gene expression profiles using microarrays.
• Performed bone marrow transplantation experiments.
• Investigated ANGPTL4's mechanism in human colon epithelial cells.

Main Results:

• ANGPTL4 deficiency exacerbated DSS- or stearic acid-induced colonic inflammation.
• Gene expression profiles in ANGPTL4^-/- mice resembled inflamed ulcerative colitis (UC), unlike ANGPTL4^+/+ mice.
• Colonic ANGPTL4 intrinsically regulates leukocyte infiltration.
• ANGPTL4 upregulates tristetraprolin expression via CREB and NF-κB, stabilizing chemokines.

Conclusions:

• ANGPTL4 protects against acute colonic inflammation; its absence worsens inflammation severity.
• ANGPTL4 is a potential therapeutic target for attenuating colonic inflammation.