Open Accessm6A-induced lncRNA MALAT1 aggravates renal fibrogenesis in obstructive nephropathy through the miR-145/FAK pathway
Author(s) -
Peihua Liu,
Bo Zhang,
Zhi Chen,
Yao He,
Yongchao Du,
Yuhang Liu,
Xiang Chen
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.102950
Subject(s) - malat1 , medicine , nephropathy , cancer research , endocrinology , downregulation and upregulation , chemistry , long non coding rna , biochemistry , gene , diabetes mellitus
Renal fibrosis is a key factor in chronic kidney disease (CKD). Long non-coding RNAs (lncRNAs) play important roles in the physiological and pathological progression of human diseases. However, the roles and underlying mechanisms of lncRNAs in renal fibrosis still need to be discovered. In this study, we first displayed the increased lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in renal fibrosis in patients with obstructive nephropathy (ON). Then we found that transforming growth factor beta 1 (TGF-β1) induced epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) protein deposition, which promoted the viability, proliferation and migration of human renal proximal tubular epithelial (HK2) cells. Next, MALAT1/miR-145/focal adhesion kinase (FAK) pathway was confirmed to play an importment role in TGF-β1-induced renal fibrosis. In addition, the MALAT1/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-β1-induced renal fibrosis in vitro and in vivo . Furthermore, m 6 A methyltransferase methyltransferase-like 3 (METTL3) was shown to be the main methyltransferase of m 6 A modification on MALAT1.