The Role of KLF4 in Lps-Induced Intestinal Epithelial Cell Injury Through the MIR-1306-5P/HIPK2 Signaling Axis

Area of Science:

• Gastroenterology
• Molecular Biology
• Cell Biology

Background:

• Sepsis-induced acute intestinal cell injury impairs intestinal barrier function, causing systemic inflammation and organ dysfunction.
• Understanding the molecular mechanisms underlying this injury is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of Kruppel-like factor 4 (KLF4) in lipopolysaccharide (LPS)-induced intestinal epithelial cell injury.
• To elucidate the molecular mechanism involving KLF4, microRNA (miR)-1306-5p, and homeodomain interacting protein kinase 2 (HIPK2).

Main Methods:

• Established an LPS-induced intestinal epithelial injury model using a human colonic mucosal epithelial cell line.
• Utilized real-time quantitative PCR and Western blot to analyze KLF4, miR-1306-5p, and HIPK2 expression.
• Assessed cell injury, apoptosis, barrier function markers (Occludin, ZO-1), and cell permeability. Investigated molecular interactions via binding assays and co-experiments.

Main Results:

• LPS treatment downregulated KLF4 and HIPK2 while upregulating miR-1306-5p.
• KLF4 overexpression enhanced cell viability, reduced apoptosis, and improved barrier function.
• KLF4 suppressed miR-1306-5p expression, leading to increased HIPK2 expression, thereby protecting against LPS-induced injury.

Conclusions:

• KLF4 plays a protective role in LPS-induced intestinal epithelial cell injury.
• The protective mechanism involves the KLF4/miR-1306-5p/HIPK2 axis, highlighting a novel therapeutic target.