Matrix metalloproteinase-7 promotes chronic kidney disease progression via the induction of inflammasomes and the suppression of autophagy

Cai Mei Zheng, Kuo Cheng Lu, Yi Jie Chen, Chia Yi Li, Yu Hsuan Lee, Hui Wen Chiu

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Deposition of extracellular matrix (ECM), epithelial-mesenchymal transition (EMT) and inflammation are crucial processes in chronic kidney disease (CKD) progression. The matrix metalloproteinases (MMPs) belong to a major enzyme group of proteinases that are involved in ECM degradation. MMP controls multiple biological processes, such as cell proliferation, EMT and apoptosis. The present study identified the roles of MMP7 in CKD progression. We demonstrated the transcriptional profiles of MMPs in kidney tissues of CKD patients in the Gene Expression Omnibus (GEO) data repository. MMP7 mRNA level was markedly upregulated in kidney tissues of CKD patients. MMP7 overexpression activated the NLRP3 and NLRP6 inflammasomes and increased fibrosis-related proteins in kidney cells. MMP7 inhibited oxidative stress-induced apoptosis and rapamycin-induced autophagy. We found that MMP7 expression in the kidney was increased in various CKD animal models. Knockdown of MMP7 affected renal function and renal fibrosis in a folic acid-induced CKD model. The inhibition of MMP7 decreased fibrosis and NLRP3 and NLRP6 inflammasomes and induced autophagy in kidney tissues. Taken together, these results provide insight into targeting MMP7 as a therapeutic strategy for CKD.

Original languageEnglish
Article number113565
JournalBiomedicine and Pharmacotherapy
Volume154
DOIs
Publication statusPublished - Oct 2022

Keywords

  • Autophagy
  • Chronic kidney disease
  • Inflammasome
  • Matrix metalloproteinase-7
  • Renal fibrosis

ASJC Scopus subject areas

  • Pharmacology

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