Research Paper Volume 12, Issue 6 pp 5280—5299

m6A-induced lncRNA MALAT1 aggravates renal fibrogenesis in obstructive nephropathy through the miR-145/FAK pathway

Peihua Liu 1, *, , Bo Zhang 1, *, , Zhi Chen 1, , Yao He 1, , Yongchao Du 1, , Yuhang Liu 1, , Xiang Chen 1, ,

  • 1 Department of Urology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, PR China
* Equal contribution

received: August 25, 2019 ; accepted: March 9, 2020 ; published: March 23, 2020 ;

https://doi.org/10.18632/aging.102950
How to Cite

Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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, m6A methyltransferase methyltransferase-like 3 (METTL3) was shown to be the main methyltransferase of m6A modification on MALAT1.

Abbreviations

CKD: chronic kidney disease; lncRNA: long non-coding RNA; MALAT1: metastasis-associated lung adenocarcinoma transcript 1; ON: obstructive nephropathy; TGF-β1: transforming growth factor beta 1; EMT: epithelial-mesenchymal transition; ECM: extracellular matrix; FAK: focal adhesion kinase; DHA: dihydroartemisinin; METTL3: methyltransferase-like 3; PFD: pirfenidone; HE: haematoxylin and eosin; IHC: immunohistochemistry; UUO: unilateral ureteral obstruction; Scr: serum creatinine; GFR: glomerular filtration rate; EPCs: endothelial progenitor cells.