Alteration of zonula occludens-1 (zo-1) in acute kidney injury in severe malaria

Abstract

Background: Zonula occludens-1 (ZO-1) proteins are scaffolding proteins providing the permeability barrier at the cytoplasmic surface of intercellular junctions. Maintenance of cell junction is important to balance the fluids and substances between compartments. In Plasmodium falciparum malaria, AKI is a major complication causing fatality and it will be valuable to investigate Z0-1 in kidney tissues and endothelial cells (ECs) in severe P. falciparum malaria. Methods: Using immunohistochemistry, paraffin-embedded kidney tissues of fetal malaria were stained with rabbit polyclonal anti-ZO-1. For immunofluorescence, ZO-1 was demonstrated in ECs-malaria parasite coculture. The expression of ZO-1 and degree of intensity were compared. Results: Significant decreased in ZO-1 expression of AKI and non-AKI cases was observed in comparison to control kidney samples (21.8 ± 4.3, 85.9 ± 10.8 vs 171.4 ± 17.5; p 0.001, p = 0.006, respectively). AKI cases also showed significant decreased in ZO-1 expression as compared to non-AKI cases (p 0.001). Immunofluorescence study showed significant alteration of ECs tight junction in malaria cases when compared with control. Conclusions: The loss of protein tight junction (ZO-1) is associated with AKI. This is confirmed by alteration of ECs tight junction demonstrated in ECs-malaria parasite co-culture system.