title: Glomerular changes and alterations of zonula occludens-1 in the kidneys of Plasmodium falciparum malaria patients.
abstract: BACKGROUND
  The process of cytoadhesion in Plasmodium falciparum malaria infection causes signaling processes that lead to structural and functional changes at the cellular level. Histopathological changes of acute kidney injury (AKI) in P. falciparum malaria often involve glomerular proliferation, thickening of the glomerular basement membrane, acute tubular necrosis, and interstitial inflammation. Focusing on the glomeruli, this study aimed to investigate glomerular and tight junction-associated protein- zonula occludens-1 (ZO-1) changes in P. falciparum malaria patients.
  
  
  METHODS
  Kidney tissues were grouped into P. falciparum with AKI (Cr ≥ 265 μmol/L or 3 mg/dl), P. falciparum without AKI (Cr < 265 μmol/L), and normal kidney tissues (control group). Glomerular cells and the glomerular area were quantified and compared in three experimental groups. The tight junction was investigated immunohistochemically using tight junction-associated protein, ZO-1, protein marker. A further immunofluorescence study was performed in an endothelial cell (EC)-parasitized red blood cell (PRBC) co-culture system, to evaluate the tight junction protein.
  
  
  RESULTS
  Glomerular cell proliferation was significant in P. falciparum with AKI (Cr ≥ 265 μmol/L). By contrast, the glomerular area decreased significantly. ZO-1 expression was significantly decreased in the AKI group compared with normal kidneys, and in kidney tissues without AKI (p < 0.05). This was further confirmed by the depletion in ZO-1 localization in ECs co-cultured with PRBCs.
  
  
  CONCLUSIONS
  In P. falciparum malaria with AKI, the decrease in glomerular area, despite glomerular cell proliferation, could be due to the collapse of cellular structures secondary to damaged tight junction-associated protein, ZO-1.
authors.forename: Benjamas
authors.initials: B
authors.lastname: Wichapoon
authors.forename: Chuchard
authors.initials: C
authors.lastname: Punsawad
authors.forename: Urai
authors.initials: U
authors.lastname: Chaisri
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand. parnpen.vir@mahidol.ac.th.
authors.forename: Parnpen
authors.initials: P
authors.lastname: Viriyavejakul
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology*; D000328:Adult; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology*; D016778:Malaria, Falciparum / Q000150:complications*; D008297:Male; D008853:Microscopy; D019108:Tight Junctions / Q000473:pathology*; D055815:Young Adult