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.
Highlights
As a global epidemic, chronic kidney disease (CKD) has severe personal and societal consequences [1]
Immunohistochemistry (IHC) staining analyses revealed that α-SMA and extracellular matrix (ECM) deposition were increased in samples from patients with fibrosis compared with those in normal tissue samples (Figure 1B). qPCR analyses illustrated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression was increased in renal fibrosis tissues compared to that in normal tissues (Figure 1C)
We proposed that MALAT1 might play an important role in mediating the effects of Transforming growth factor-β1 (TGF-β1) in HK2 cells
Summary
Chronic kidney disease (CKD) has severe personal and societal consequences [1]. Obstructive nephropathy (ON) is the renal disease caused by impaired flow of urine or tubular fluid, which refers to the presence of structural or functional changes in the urinary tract that impede the normal flow of urine [2]. Obstructive uropathy, which can lead to ON without timely intervention, is the main cause of CKD. Fibrosis is a hallmark of CKD and affects both the glomeruli and the tubules as well as causes renal vasculature alterations [4]. Considering the role of renal fibrosis in CKD with ON, we believe that understanding the formation, reversal and underlying mechanism of renal fibrosis could provide valuable insights and opportunities for improving monitoring techniques and therapeutic interventions for CKD caused by ON or even for other diseases
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