Prolonged oleic acid exposure impairs Caco-2 cell differentiation and tight junction integrity

Area of Science:

• Gastroenterology
• Cell Biology
• Molecular Biology

Background:

• Intestinal homeostasis relies on the proliferation to differentiation transition (PDT) of epithelial cells.
• Disruptions in PDT are linked to systemic diseases.
• High-fat diets (HFD) can cause systemic inflammation via intestinal barrier permeabilization, potentially by affecting tight junctions (TJs) during enterocyte differentiation.

Purpose of the Study:

• To investigate the effects of oleic acid (OA), a major HFD component, on Caco-2 cell differentiation and intestinal barrier function.

Main Methods:

• Caco-2 cells were exposed to varying concentrations of OA (0.2-1.6 mM) for 6 hours daily over 10-21 days.
• Assessed time-dependent changes in cell differentiation markers, monolayer permeability (transepithelial electrical resistance), TJ protein levels (ZO-1, claudin-1), TJ dynamics, and redox homeostasis.

Main Results:

• OA exposure altered intestinal barrier formation, indicated by reduced transepithelial electrical resistance.
• OA decreased levels of key TJ proteins ZO-1 and claudin-1.
• OA activated signaling pathways (ERK1/2, NF-κB, MLC phosphorylation) leading to TJ opening and altered redox homeostasis.

Conclusions:

• Prolonged OA exposure disrupts Caco-2 cell differentiation into mature enterocytes.
• OA's effects on TJ integrity and function contribute to intestinal barrier permeabilization.
• These findings provide a molecular mechanism linking HFD consumption to intestinal barrier dysfunction and systemic inflammation.