title: Significance of the urokinase-type plasminogen activator and its receptor in the progression of focal segmental glomerulosclerosis in clinical and mouse models.
abstract: BACKGROUND
  suPAR biomarker generally considered a pathogenic factor in FSGS. However, studies have been published that dispute this conclusion. The current study was designed to investigate the roles of uPA and suPAR in FSGS in clinical and mouse models.
  
  
  METHODS
  Clinical subjects including those with biopsy-proven FSGS and MCD were enrolled. To verify the role of uPA in FSGS, Adriamycin was used to induce FSGS in uPA knockout (uPA(-/-)) and BALB/c (WT) mice. Proteinuria and suPAR, the cleaved/intact forms of the circulating suPAR, and possible proteases involving cleavage of the suPAR were also studied.
  
  
  RESULTS
  FSGS clinical cases presented significantly higher serum levels of suPAR and Cr and lower serum levels of uPA. In the mice model, the uPA(-/-) group exhibited faster disease progression and worsening proteinuria than the WT group. In addition, the uPA(-/-) group had higher plasma suPAR levels, glomerular cell apoptosis, and dysregulation of the Th1/Th2 balance. In an analysis of suPAR variants in FSGS, both the intact and cleaved forms of the suPAR were higher in clinical subjects and the mouse model. However, the process of suPAR cleavage was not mediated by enzymatic activities of the uPA, elastase, or cathepsin G.
  
  
  CONCLUSIONS
  A deficiency of uPA accelerated the progression of Adriamycin-induced mouse FSGS model. Decrease of serum uPA levels may be an indicator of the progression of FSGS in clinical subjects and animal models.
authors: Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Chenggong Road, Neihu District, Taipei, 114, Taiwan.
authors: Jin-Shuen
authors: JS
authors: Chen
authors: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
authors: Li-Chien
authors: LC
authors: Chang
authors: Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors: Chung-Ze
authors: CZ
authors: Wu
authors: Biomedical Technology & Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors: Tzu-Ling
authors: TL
authors: Tseng
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, No. 250, Wu-Xing Street, Taipei, 110, Taiwan.
authors: Jui-An
authors: JA
authors: Lin
authors: Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, No. 250, Wu-Xing Street, Taipei, 110, Taiwan.
authors: Yuh-Feng
authors: YF
authors: Lin
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, No. 250, Wu-Xing Street, Taipei, 110, Taiwan. ccheng@tmu.edu.tw.|Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. ccheng@tmu.edu.tw.
authors: Chao-Wen
authors: CW
authors: Cheng
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator