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

研究成果: 雜誌貢獻文章同行評審

8 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號242
期刊Journal of Biomedical Science
23
發行號1
DOIs
出版狀態已發佈 - 2月 4 2016

ASJC Scopus subject areas

  • 內分泌學、糖尿病和代謝
  • 分子生物學
  • 臨床生物化學
  • 細胞生物學
  • 生物化學(醫學)
  • 藥學(醫學)

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