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

Author:

Zhou Zheng,Wu Lei,Zhao Sheng,Xia Shu-Jie,Pan Lei,Chen Min,Zhu Yi-Ping,Jiang Jun-Tao,Shi Fei

Abstract

Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.

Publisher

S. Karger AG

Subject

Geriatrics and Gerontology,Aging

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