American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Dec 2020
Silencing of the lncRNA TUG1 attenuates the epithelial-mesenchymal transition of renal tubular epithelial cells by sponging miR-141-3p via regulating β-catenin.
Renal interstitial fibrosis (RIF) is characterized by excessive extracellular matrix deposition and involves epithelial-mesenchymal transition (EMT). The lncRNA taurine-upregulated gene 1 (TUG1) participates in EMT in several cancers; however, the effect and underlying mechanism of TUG1 in RIF-related EMT remain unclear. Here, we explored the mechanisms by which TUG1 modulates RIF. ⋯ TUG1 directly targeted miR-141-3p, and miR-141-3p was directly bound to CTNNB1. Downregulation of miR-141-3p inhibited TUG1 silencing-induced suppression of EMT. In conclusion, TUG1 promotes EMT in TGF-β1-induced HK-2 cells via upregulation of β-catenin levels by sponging miR-141-3p, suggesting a novel therapeutic candidate for RIF.
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Am. J. Physiol. Renal Physiol. · Dec 2020
Overexpression of TGF-β1 induces renal fibrosis and accelerates the decline in kidney function in polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of numerous fluid-filled cysts, extensive fibrosis, and the progressive decline in kidney function. Transforming growth factor-β1 (TGF-β1), an important mediator for renal fibrosis and chronic kidney disease, is overexpressed by cystic cells compared with normal kidney cells; however, its role in PKD pathogenesis remains undefined. To investigate the effect of TGF-β1 on cyst growth, fibrosis, and disease progression, we overexpressed active TGF-β1 specifically in collecting ducts (CDs) of phenotypic normal (Pkd1RC/+) and Pkd1RC/RC mice. ⋯ In Pkd1RC/RC mice, CD overexpression of TGF-β1 increased cyst epithelial cell proliferation. However, extensive fibrosis limited cyst enlargement and caused contraction of the kidneys, leading to a loss of renal function and a shortened lifespan of the mice. These data demonstrate that TGF-β1-induced fibrosis constrains cyst growth and kidney enlargement and accelerates the decline of renal function, supporting the hypothesis that a combined therapy that inhibits renal cyst growth and fibrosis will be required to effectively treat ADPKD.