Significance of the urokinase-type plasminogen activator and its receptor in the progression of focal segmental glomerulosclerosis in clinical and mouse models

Jin Shuen Chen, Li Chien Chang, Chung-Ze Wu, Tzu Ling Tseng, Jui-An Lin, Yuh-Feng Lin, Chao-Wen Cheng

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4 Citations (Scopus)

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.

Original languageEnglish
Article number242
JournalJournal of Biomedical Science
Volume23
Issue number1
DOIs
Publication statusPublished - Feb 4 2016

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Urokinase Plasminogen Activator Receptors
Focal Segmental Glomerulosclerosis
Proteinuria
Doxorubicin
Serum
Th1-Th2 Balance
Cathepsin G
Dissent and Disputes
Biopsy
Pancreatic Elastase
Biomarkers
Disease Progression
Animals
Peptide Hydrolases
Animal Models
Apoptosis
Plasmas

Keywords

  • Focal and segmental glomerulosclerosis
  • Soluble urokinase-type plasminogen activator receptor
  • Th1/Th2 balance
  • Urokinase-type plasminogen activator

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

@article{acfc5b4dcfa54d3081e3172498509163,
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.",
keywords = "Focal and segmental glomerulosclerosis, Soluble urokinase-type plasminogen activator receptor, Th1/Th2 balance, Urokinase-type plasminogen activator",
author = "Chen, {Jin Shuen} and Chang, {Li Chien} and Chung-Ze Wu and Tseng, {Tzu Ling} and Jui-An Lin and Yuh-Feng Lin and Chao-Wen Cheng",
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T1 - Significance of the urokinase-type plasminogen activator and its receptor in the progression of focal segmental glomerulosclerosis in clinical and mouse models

AU - Chen, Jin Shuen

AU - Chang, Li Chien

AU - Wu, Chung-Ze

AU - Tseng, Tzu Ling

AU - Lin, Jui-An

AU - Lin, Yuh-Feng

AU - Cheng, Chao-Wen

PY - 2016/2/4

Y1 - 2016/2/4

N2 - 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.

AB - 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.

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