Skip to main content
eScholarship
Open Access Publications from the University of California

The Matrix Metalloproteinase-13 Inhibitor Poricoic Acid ZI Ameliorates Renal Fibrosis by Mitigating Epithelial-Mesenchymal Transition.

  • Author(s): Chen, Lin
  • Cao, Gang
  • Wang, Ming
  • Feng, Ya-Long
  • Chen, Dan-Qian
  • Vaziri, Nosratola D
  • Zhuang, Shougang
  • Zhao, Ying-Yong
  • et al.
Abstract

SCOPE:Fibrosis plays a key role in the progression of various diseases. Matrix metalloproteinases (MMPs) are important for epithelial-mesenchymal transition (EMT), which contributes to organ fibrosis. We identified four new poricoic acids, poricoic acid ZI, ZJ, ZK and ZL, as novel MMP inhibitors from edible mushroom Poria cocos. METHODS:Molecular docking, siRNA techniques, TGF-β1-treated renal cells and unilateral ureteral obstructed (UUO) mice were used to explore the potential efficacy of the novel MMP inhibitors in mitigating the fibrotic process. RESULTS:Treatment with four poricoic acids downregulated profibrotic protein expression in TGF-β1-induced HK-2 cells. Similar results were observed in NRK-52E and NRK-49F cells, indicating that poricoic acids can suppress EMT. Furthermore, both in vitro and in vivo experiments demonstrated that poricoic acid ZI (PZI) exerts a stronger inhibitory effect on protein expression and enzymatic activity of MMP-13 than the other three compounds, which was consistent with the docking results. The inhibitory effect of PZI on MMP-13 was partially attenuated by MMP-13 RNAi in HK-2 cells and UUO mice. CONCLUSIONS:The findings indicate that as a specific MMP-13 inhibitor, PZI attenuates EMT and renal fibrosis. Therefore, the MMP-13 inhibitor PZI could be a novel therapeutic candidate for limiting EMT and renal fibrosis. This article is protected by copyright. All rights reserved.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View