Upregulation of AQP2 mediated by transcription factor FOXO1 inhibits TGF‑β‑induced fibrosis in human urothelial cells

Qiu,Yue; Qiu,Yue; Xing,Zhaoquan; Guo,Zhaoxin; Liu,Zhaoxu

doi:10.3892/etm.2021.10824

Upregulation of AQP2 mediated by transcription factor FOXO1 inhibits TGF‑β‑induced fibrosis in human urothelial cells

Authors:
- Yue Qiu
- Zhaoquan Xing
- Zhaoxin Guo
- Zhaoxu Liu
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Affiliations: Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: September 30, 2021 https://doi.org/10.3892/etm.2021.10824
Article Number: 1388
Copyright: © Qiu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bladder outlet obstruction (BOO) is a common urological disease, and inhibition of TGF‑β‑induced bladder tissue fibrosis may serve as an alternative strategy for BOO treatment. Aquaporin (AQP)2 was reported to be aberrantly expressed in rat BOO, but its specific role was not clarified. The aim of the present study was to explore the role of AQP2 in TGF‑β‑induced urothelial cell fibrosis and elucidate the potential underlying mechanism. The SV‑HUC‑1 human urinary tract epithelial cell line was treated with TGF‑β1 to establish an in vitro model of bladder fibrosis. Cell Counting Kit‑8 and wound healing assays were performed to measure cell viability and migration, respectively. Cell transfection was conducted to silence/overexpress AQP2 and Forkhead box O1 (FOXO1). Protein expression was measured using western blotting. Luciferase reporter and chromatin immunoprecipitation assays were used to verify the predicted interaction between AQP2 and FOXO1. The present study found that AQP2 expression was downregulated in TGF‑β1‑treated urothelial cells. Overexpression of AQP2 significantly suppressed cell viability, migration and epithelial‑to‑mesenchymal transition in TGF‑β1‑treated SV‑HUC‑1 cells. In addition, FOXO1 overexpression exerted similar effects as AQP2 overexpression on TGF‑β‑treated SV‑HUC‑1 cells, but these changes were partially abolished by AQP2 knockdown. It was also found that FOXO1 was able to bind to the AQP2 promoter and regulate AQP2 expression. In conclusion, the transcription factor FOXO1 may upregulate AQP2 expression, thereby inhibiting TGF‑β‑induced fibrosis in human urothelial cells. The findings of the present study may provide a novel potential strategy for the clinical treatment of BOO by targeting AQP2.

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