Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis

Area of Science:

• Gastroenterology
• Cell Biology
• Physiology

Background:

• The mechanisms driving diarrhea in ulcerative colitis (UC) remain poorly understood.
• Previous assessments may have underestimated the extent of epithelial barrier dysfunction in UC.

Purpose of the Study:

• To functionally and structurally characterize the epithelial barrier and transport properties in the inflamed colon of UC patients.
• To elucidate the role of tight junctions in UC-related barrier defects.

Main Methods:

• Alternating current impedance analysis was used to measure pure epithelial resistance in sigmoid colon tissues from UC patients.
• Freeze-fracture electron microscopy was employed to examine the structure of tight junctions (TJs) in epithelial cells.

Main Results:

• Impedance analysis revealed a significant decrease in epithelial resistance (95 to 20 omega3. cm2) in UC, masked by increased subepithelial resistance due to inflammation.
• UC colonic epithelium showed a marked reduction in TJ strand count (surface: 6.94 to 4.76; crypts: 7.26 to 5.46).
• These findings indicate a substantial impairment of the intestinal barrier function in UC.

Conclusions:

• The inflamed colonic mucosa in UC exhibits a more pronounced barrier defect than previously recognized.
• Alterations in tight junction structure contribute significantly to this barrier defect.
• Increased permeability (leak-flux) due to impaired barrier function likely plays a key role in UC-associated diarrhea.