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Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway
Benign prostatic hyperplasia (BPH) is a common disease in elderly men with an uncertain etiology and mechanistic basis. Metabolic syndrome (MetS) is also a very common illness and is closely related to BPH. Simvastatin (SV) is one of the widely used statins for MetS. Peroxisome-proliferator-activate...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003121/ https://www.ncbi.nlm.nih.gov/pubmed/36902342 http://dx.doi.org/10.3390/ijms24054911 |
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author | Wang, Zhen Yang, Shu Li, Yan Zhou, Yongying Liu, Daoquan Liu, Jianmin DiSanto, Michael E. Zhang, Xinhua |
author_facet | Wang, Zhen Yang, Shu Li, Yan Zhou, Yongying Liu, Daoquan Liu, Jianmin DiSanto, Michael E. Zhang, Xinhua |
author_sort | Wang, Zhen |
collection | PubMed |
description | Benign prostatic hyperplasia (BPH) is a common disease in elderly men with an uncertain etiology and mechanistic basis. Metabolic syndrome (MetS) is also a very common illness and is closely related to BPH. Simvastatin (SV) is one of the widely used statins for MetS. Peroxisome-proliferator-activated receptor gamma (PPARγ), crosstalking with the WNT/β-catenin pathway, plays important roles in MetS. Our current study aimed to examine SV-PPARγ-WNT/β-catenin signaling in the development of BPH. Human prostate tissues and cell lines plus a BPH rat model were utilized. Immunohistochemical, immunofluorescence, hematoxylin and eosin (H&E) and Masson’s trichrome staining, construction of a tissue microarray (TMA), ELISA, CCK-8 assay, qRT-PCR, flow cytometry, and Western blotting were also performed. PPARγ was expressed in both prostate stroma and epithelial compartments and downregulated in BPH tissues. Furthermore, SV dose-dependently triggered cell apoptosis and cell cycle arrest at the G0/G1 phase and attenuated tissue fibrosis and the epithelial–mesenchymal transition (EMT) process both in vitro and in vivo. SV also upregulated the PPARγ pathway, whose antagonist could reverse SV produced in the aforementioned biological process. Additionally, crosstalk between PPARγ and WNT/β-catenin signaling was demonstrated. Finally, correlation analysis with our TMA containing 104 BPH specimens showed that PPARγ was negatively related with prostate volume (PV) and free prostate-specific antigen (fPSA) and positively correlated with maximum urinary flow rate (Qmax). WNT-1 and β-catenin were positively related with International Prostate Symptom Score (IPSS) and nocturia, respectively. Our novel data demonstrate that SV could modulate cell proliferation, apoptosis, tissue fibrosis, and the EMT process in the prostate through crosstalk between PPARγ and WNT/β-catenin pathways. |
format | Online Article Text |
id | pubmed-10003121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100031212023-03-11 Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway Wang, Zhen Yang, Shu Li, Yan Zhou, Yongying Liu, Daoquan Liu, Jianmin DiSanto, Michael E. Zhang, Xinhua Int J Mol Sci Article Benign prostatic hyperplasia (BPH) is a common disease in elderly men with an uncertain etiology and mechanistic basis. Metabolic syndrome (MetS) is also a very common illness and is closely related to BPH. Simvastatin (SV) is one of the widely used statins for MetS. Peroxisome-proliferator-activated receptor gamma (PPARγ), crosstalking with the WNT/β-catenin pathway, plays important roles in MetS. Our current study aimed to examine SV-PPARγ-WNT/β-catenin signaling in the development of BPH. Human prostate tissues and cell lines plus a BPH rat model were utilized. Immunohistochemical, immunofluorescence, hematoxylin and eosin (H&E) and Masson’s trichrome staining, construction of a tissue microarray (TMA), ELISA, CCK-8 assay, qRT-PCR, flow cytometry, and Western blotting were also performed. PPARγ was expressed in both prostate stroma and epithelial compartments and downregulated in BPH tissues. Furthermore, SV dose-dependently triggered cell apoptosis and cell cycle arrest at the G0/G1 phase and attenuated tissue fibrosis and the epithelial–mesenchymal transition (EMT) process both in vitro and in vivo. SV also upregulated the PPARγ pathway, whose antagonist could reverse SV produced in the aforementioned biological process. Additionally, crosstalk between PPARγ and WNT/β-catenin signaling was demonstrated. Finally, correlation analysis with our TMA containing 104 BPH specimens showed that PPARγ was negatively related with prostate volume (PV) and free prostate-specific antigen (fPSA) and positively correlated with maximum urinary flow rate (Qmax). WNT-1 and β-catenin were positively related with International Prostate Symptom Score (IPSS) and nocturia, respectively. Our novel data demonstrate that SV could modulate cell proliferation, apoptosis, tissue fibrosis, and the EMT process in the prostate through crosstalk between PPARγ and WNT/β-catenin pathways. MDPI 2023-03-03 /pmc/articles/PMC10003121/ /pubmed/36902342 http://dx.doi.org/10.3390/ijms24054911 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Zhen Yang, Shu Li, Yan Zhou, Yongying Liu, Daoquan Liu, Jianmin DiSanto, Michael E. Zhang, Xinhua Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway |
title | Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway |
title_full | Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway |
title_fullStr | Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway |
title_full_unstemmed | Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway |
title_short | Simvastatin Improves Benign Prostatic Hyperplasia: Role of Peroxisome-Proliferator-Activated Receptor-γ and Classic WNT/β-Catenin Pathway |
title_sort | simvastatin improves benign prostatic hyperplasia: role of peroxisome-proliferator-activated receptor-γ and classic wnt/β-catenin pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003121/ https://www.ncbi.nlm.nih.gov/pubmed/36902342 http://dx.doi.org/10.3390/ijms24054911 |
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