Upregulation of FGF7 Induced Intravesical Prostatic Protrusion of Benign Prostatic Hyperplasia via the ERK1/2 Signaling Pathway.

Humans Male Prostatic Hyperplasia / drug therapy Prostate / metabolism Up-Regulation MAP Kinase Signaling System Urinary Bladder Neck Obstruction / complications Fibroblast Growth Factor 7 / genetics
Benign prostatic hyperplasia ERK signaling Epithelial-mesenchymal transition Intravesical prostatic protrusion RNA sequencing

Journal

Gerontology
ISSN: 1423-0003
Titre abrégé: Gerontology
Pays: Switzerland
ID NLM: 7601655

Informations de publication

Date de publication:
2023
Historique:
received: 31 12 2021
accepted: 19 10 2022
medline: 1 6 2023
pubmed: 25 1 2023
entrez: 24 1 2023
Statut: ppublish

Résumé

Intravesical prostatic protrusion (IPP) has been reported to be associated with bladder outlet obstruction and is the main cause of lower urinary tract symptoms (LUTS) during the development of benign prostatic hyperplasia (BPH). However, the molecular mechanism of IPP remains unclear. Clinical data analysis was performed to analyze the association between IPP and long-term complications in patients with BPH. RNA sequencing was performed on prostate tissues (IPP or not). Stromal cells were obtained from IPP-derived primary cultures to explore the molecular mechanism of IPP formation. Cell proliferation was evaluated by a CCK-8 assay. Multiple proteins in the signaling pathway were assessed using Western blot. First, we confirmed that IPP is a prognostic factor for long-term complications in patients with BPH. Then, we observed that FGF7 was upregulated in both IPP tissues and IPP primary stromal cells through immunohistochemistry, Western blot, and quantitative real-time PCR. Furthermore, FGF7 was significantly upregulated in high IPP-grade prostate tissues. The coculture experiments showed that the downregulation of FGF7 in IPP-derived stromal cells inhibited the proliferation and migration of the prostate epithelial cells. Additionally, FGF7 was bound to FGFR2 to induce the epithelial-mesenchymal transition process through binding to FGFR2. RNA sequencing analysis also revealed the activation of the MAPK/ERK1/2 signaling pathway. The MAPK/ERK1/2 was downregulated by a specific inhibitor affecting the FGF7 stimulation in vitro. Our data reveal a novel amplification effect, i.e., stromal cell-derived FGF7 promotes epithelial cell proliferation and stromal cell phenotype, ultimately inducing IPP formation. Targeting FGF7 can significantly reduce epithelial to stromal transition and provide a potential therapeutic target for BPH progression.

Identifiants

DOI: 10.1159/000527929 PMID: 36693332
pubmed: 36693332
pii: 000527929
doi: 10.1159/000527929
doi:

Substances chimiques

FGF7 protein, human 0
Fibroblast Growth Factor 7 126469-10-1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

615-627

Informations de copyright

© 2023 S. Karger AG, Basel.

Auteurs

Zheng Zhou (Z)

Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai, China.

Lei Wu (L)

Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai, China.

Sheng Zhao (S)

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Urology, Shanghai Jiao Tong University, Shanghai, China.

Shu-Jie Xia (SJ)

Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai, China.
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Urology, Shanghai Jiao Tong University, Shanghai, China.

Lei Pan (L)

Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai, China.

Min Chen (M)

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Yi-Ping Zhu (YP)

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Urology, Shanghai Jiao Tong University, Shanghai, China.

Jun-Tao Jiang (JT)

Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai, China.
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Urology, Shanghai Jiao Tong University, Shanghai, China.

Fei Shi (F)

Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai, China.
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Urology, Shanghai Jiao Tong University, Shanghai, China.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Upregulation of FGF7 Induced Intravesical...
questionsmedicales.fr › Maladies urogénitales › Maladies urogénitales de l'homme › Maladies de l'appareil génital mâle › Maladies de la prostate › Hyperplasie de la prostate › Upregulation of FGF7 Induced Intravesical...
questionsmedicales.fr › Tissus › Glandes exocrines › Prostate › Upregulation of FGF7 Induced Intravesical...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › Upregulation of FGF7 Induced Intravesical...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Système de signalisation des MAP kinases › Upregulation of FGF7 Induced Intravesical...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Maladies de la vessie › Obstruction du col de la vessie › Upregulation of FGF7 Induced Intravesical...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance fibroblastique › Facteur de croissance fibroblastique de type 7 › Upregulation of FGF7 Induced Intravesical...