TY - JOUR
T1 - S100A4 modulates cell proliferation, apoptosis and fibrosis in the hyperplastic prostate
AU - Yang, Liang
AU - Liu, Jiang
AU - Yin, Jing
AU - Li, Yan
AU - Liu, Jianmin
AU - Liu, Daoquan
AU - Wang, Zhen
AU - DiSanto, Michael E.
AU - Zhang, Weibing
AU - Zhang, Xinhua
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/4
Y1 - 2024/4
N2 - Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men worldwide that may result in lower urinary tract symptoms (LUTS). At present, the specific pathophysiological mechanism for BPH/LUTS LUTS remains unclear. S100 calcium binding protein A4 (S100A4), a member of the calcium binding protein family, regulates a variety of biological processes including cell proliferation, apoptosis and fibrosis. The aim of the current study was to explore and clarify the possible role of S100A4 in BPH/LUTS. The human prostate stromal cell line (WPMY-1), rat prostate epithelial cells, human prostate tissues and two BPH rat models were employed in this study. The expression and localization of S100A4 were detected by quantitative real time PCR (qRT-PCR), immunofluorescence microscopy, Western blotting and immunohistochemistry analysis. Also, S100A4 knockdown or overexpression cell models were constructed and a BPH rat model was induced with testosterone propionate (T) or phenylephrine (PE). The BPH animals were treated with Niclosamide, a S100A4 transcription inhibitor. Results demonstrated that S100A4 was mainly localized in human prostatic stroma and rat prostatic epithelium, and showed a higher expression in BPH. Knockdown of S100A4 induced cell apoptosis, cell proliferation arrest and a reduction of tissue fibrosis markers. Overexpression of S100A4 reversed the aforementioned changes. We also demonstrated that S100A4 regulated proliferation and apoptosis mainly through the ERK pathway and modulated fibrosis via Wnt/β-catenin signaling. In conclusion, our novel data demonstrate that S100A4 could play a crucial role in BPH development and may be explored as a new therapeutic target of BPH.
AB - Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men worldwide that may result in lower urinary tract symptoms (LUTS). At present, the specific pathophysiological mechanism for BPH/LUTS LUTS remains unclear. S100 calcium binding protein A4 (S100A4), a member of the calcium binding protein family, regulates a variety of biological processes including cell proliferation, apoptosis and fibrosis. The aim of the current study was to explore and clarify the possible role of S100A4 in BPH/LUTS. The human prostate stromal cell line (WPMY-1), rat prostate epithelial cells, human prostate tissues and two BPH rat models were employed in this study. The expression and localization of S100A4 were detected by quantitative real time PCR (qRT-PCR), immunofluorescence microscopy, Western blotting and immunohistochemistry analysis. Also, S100A4 knockdown or overexpression cell models were constructed and a BPH rat model was induced with testosterone propionate (T) or phenylephrine (PE). The BPH animals were treated with Niclosamide, a S100A4 transcription inhibitor. Results demonstrated that S100A4 was mainly localized in human prostatic stroma and rat prostatic epithelium, and showed a higher expression in BPH. Knockdown of S100A4 induced cell apoptosis, cell proliferation arrest and a reduction of tissue fibrosis markers. Overexpression of S100A4 reversed the aforementioned changes. We also demonstrated that S100A4 regulated proliferation and apoptosis mainly through the ERK pathway and modulated fibrosis via Wnt/β-catenin signaling. In conclusion, our novel data demonstrate that S100A4 could play a crucial role in BPH development and may be explored as a new therapeutic target of BPH.
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U2 - 10.1016/j.biocel.2024.106551
DO - 10.1016/j.biocel.2024.106551
M3 - Article
C2 - 38360265
AN - SCOPUS:85186522999
SN - 1357-2725
VL - 169
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
M1 - 106551
ER -