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AUF1 modulates TGF-β signal in renal tubular epithelial cells via post-transcriptional regulation of Nedd4L expression.
- Source :
-
Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2018 Jan; Vol. 1865 (1), pp. 48-56. Date of Electronic Publication: 2017 Oct 03. - Publication Year :
- 2018
-
Abstract
- Posttranscriptional regulation process plays important roles in renal disease pathogenesis. AU-rich element RNA-binding protein (AUF1) interacts with and destabilizes mRNAs containing AU-rich elements (AREs) in their 3'UTR. The current study demonstrated that AUF1 was increased in unilateral ureteral obstruction (UUO) animal models. While proliferation and migration of HK2 cells was unaltered by AUF1 downregulation under normal condition, proliferative inhibition and migratory promotion mediated by TGF-β was significantly compromised. Mechanically, AUF1 downregulation decreased phosphorylated Smad2/3 via increasing their E3 ligase Nedd4L at the posttranscriptional level. In addition, the current study identified Nedd4L as a previously unreported target of AUF1. AUF1 regulates Nedd4L expression at the posttranscriptional level by interaction with AREs in the 3'UTR of the Nedd4L mRNA. Collectively, the current study indicates that AUF1 might be a potential player in renal tubulointerstitial fibrosis through modulation of TGF-β signal transduction via posttranscriptional regulation of Nedd4L.<br /> (Copyright © 2017. Published by Elsevier B.V.)
- Subjects :
- Animals
Cells, Cultured
Epithelial Cells pathology
Gene Expression Regulation drug effects
Heterogeneous Nuclear Ribonucleoprotein D0
Humans
Kidney Tubules drug effects
Kidney Tubules pathology
Male
Nedd4 Ubiquitin Protein Ligases metabolism
RNA Interference drug effects
Rats
Rats, Sprague-Dawley
Signal Transduction drug effects
Signal Transduction genetics
Transforming Growth Factor beta pharmacology
Ureteral Obstruction genetics
Ureteral Obstruction metabolism
Ureteral Obstruction pathology
Epithelial Cells metabolism
Heterogeneous-Nuclear Ribonucleoprotein D physiology
Kidney Tubules metabolism
Nedd4 Ubiquitin Protein Ligases genetics
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0167-4889
- Volume :
- 1865
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Molecular cell research
- Publication Type :
- Academic Journal
- Accession number :
- 28986222
- Full Text :
- https://doi.org/10.1016/j.bbamcr.2017.10.001