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

• Published in: Biomedicine & pharmacotherapy 2022-10, Vol.154, p.113565-113565, Article 113565
• Main Authors: Zheng, Cai-Mei, Lu, Kuo-Cheng, Chen, Yi-Jie, Li, Chia-Yi, Lee, Yu-Hsuan, Chiu, Hui-Wen
• Format: Article
• Language: English
• Subjects: Autophagy; Chronic kidney disease; Inflammasome; Matrix metalloproteinase-7; Renal fibrosis
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113565

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. •MMP7 mRNA levels was upregulated predominantly in kidney tissues of CKD patients.•MMP7 overexpression activated the NLRP3 and NLRP6 inflammasomes in kidney cells.•MMP7 increased fibrosis-related proteins in kidney cells.•MMP7 inhibited oxidative stress-induced apoptosis and rapamycin-induced autophagy.•Knockdown of MMP7 affected renal function and renal fibrosis in a CKD mouse model.