<br>YAP1 识别炎症和机械信号，通过促进细胞存活和纤维化加剧良性前列腺增生,Advanced Science

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YAP1 识别炎症和机械信号，通过促进细胞存活和纤维化加剧良性前列腺增生
Advanced Science ( IF 14.3 ) Pub Date : 2023-12-04 , DOI: 10.1002/advs.202304274
Dongxu Lin ₁ , Changcheng Luo ₁ , Pengyu Wei ₁ , An Zhang ₂ , Mengyang Zhang ₃ , Xiaoliang Wu ₁ , Bolang Deng ₁ , Zhipeng Li ₁ , Kai Cui ₁ , Zhong Chen ₁

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慢性前列腺炎症促进细胞存活和纤维化，导致良性前列腺增生（BPH）并加重泌尿系统症状。人们正在研究 yes 相关蛋白 1 (YAP1)（一种器官大小控制器和机械转导器）是否与炎症诱导的 BPH 有关。分析了人和大鼠 BPH 标本中 YAP1 表达与纤维化之间的相关性。此外，还研究了YAP1激活对前列腺细胞存活和纤维化的影响及其潜在机制。因此，在与炎症相关的人和大鼠样本中，YAP1 总表达和核表达以及下游基因显着上调。 YAP1表达与纤维化严重程度或临床表现之间存在显着正相关。 YAP1 沉默通过减少细胞增殖和增加细胞凋亡来抑制细胞存活，并通过逆转前列腺 BPH-1 和 WPMY-1 细胞中的上皮间质转化 (EMT) 和细胞外基质 (ECM) 沉积来减轻纤维化。从机制上讲，炎症刺激和刚性基质硬度协同激活 RhoA/ROCK1 通路，引发细胞骨架重塑，从而促进 YAP1 激活，加剧 BPH 的发展。总体而言，炎症触发的机械刚度增强会激活 RhoA/ROCK1/F-actin/YAP1 轴，从而促进前列腺细胞存活和纤维化，从而加速 BPH 进展。

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YAP1 Recognizes Inflammatory and Mechanical Cues to Exacerbate Benign Prostatic Hyperplasia via Promoting Cell Survival and Fibrosis

Chronic prostatic inflammation promotes cell survival and fibrosis, leading to benign prostatic hyperplasia (BPH) with aggravated urinary symptoms. It is investigated whether yes-associated protein 1 (YAP1), an organ size controller and mechanical transductor, is implicated in inflammation-induced BPH. The correlation between YAP1 expression and fibrosis in human and rat BPH specimens is analyzed. Furthermore, the effects of YAP1 activation on prostatic cell survival and fibrosis, as well as the underlying mechanism, are also studied. As a result, total and nuclear YAP1 expression, along with downstream genes are significantly upregulated in inflammation-associated human and rat specimens. There is a significant positive correlation between YAP1 expression and the severity of fibrosis or clinical performance. YAP1 silencing suppresses cell survival by decreasing cell proliferation and increasing apoptosis, and alleviates fibrosis by reversing epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition in prostatic BPH-1 and WPMY-1 cells. Mechanistically, inflammatory stimulus and rigid matrix stiffness synergistically activate the RhoA/ROCK1 pathway to provoke cytoskeleton remodeling, thereby promoting YAP1 activation to exacerbate BPH development. Overall, inflammation-triggered mechanical stiffness reinforcement activates the RhoA/ROCK1/F-actin/YAP1 axis, thereby promoting prostatic cell survival and fibrosis to accelerate BPH progression.

更新日期：2023-12-04

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