Phosphodiesterase type 5 inhibitor tadalafil reduces prostatic fibrosis via MiR-3126-3p/FGF9 axis in benign prostatic hyperplasia.

磷酸二酯酶 5 型抑制剂他达拉非通过 MiR - 3126 - 3p / FGF9 轴减少良性前列腺增生中的前列腺纤维化.

• 影响指数: 7.173
• 发表时间: 2024 Aug 2
• 来源期刊: Biol Direct
• DOI: 10.1186/s13062-024-00504-y
• PMID: 39095835
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 生物
• 作者列表: Li T,Zhang Y,Zhou Z,Guan L,Zhang Y,Zhou Z,Wang W,Zhou X,Cui D,Jiang C,Ruan Y

关键词: Benign prostatic hyperplasia; FGF9; Myofibroblast differentiation; Phosphodiesterase 5 inhibitor; miR-3126-3p

Mesh: Male; Prostatic Hyperplasia / metabolism drug therapy genetics; MicroRNAs / genetics metabolism; Tadalafil / pharmacology; Phosphodiesterase 5 Inhibitors / pharmacology; Humans; Fibrosis; Fibroblast Growth Factor 9 / metabolism genetics; Prostate / drug effects metabolism; Myofibroblasts / metabolism drug effects; Transforming Growth Factor beta1 / metabolism genetics; Cell Proliferation / drug effects

Abstract

Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFβ1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFβ1 suppression. Overall, TGFβ1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process.

摘要

肌成纤维细胞的形成和前列腺纤维化在良性前列腺增生（BPH）的发展中起着至关重要的作用。特异性靶向肌成纤维细胞的治疗可能是治疗BPH的有希望的方法。他达拉非,5型磷酸二酯酶（PDE5）抑制剂，有可能干预这个生物过程。本研究采用前列腺基质成纤维细胞通过TGFβ1刺激诱导肌成纤维细胞分化。因此,他达拉非显着抑制前列腺基质成纤维细胞增殖和纤维化过程，与对照组相比。此外，我们的转录组测序结果显示,他达拉非抑制FGF9分泌,同时通过抑制TGFβ1改善miR-3126-3p表达.总的来说,TGFβ1可以通过前列腺基质中的miR-3126-3p触发促纤维化信号,使用他达拉非可以抑制这一过程。