Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Curr Med Sci. 2024 Aug;44(4):718-725. doi: 10.1007/s11596-024-2881-3. Epub 2024 Jun 27.
Bladder outlet obstruction (BOO) results in significant fibrosis in the chronic stage and elevated bladder pressure. Piezo1 is a type of mechanosensitive (MS) channel that directly responds to mechanical stimuli. To identify new targets for intervention in the treatment of BOO-induced fibrosis, this study investigated the impact of high hydrostatic pressure (HHP) on Piezo1 activity and the progression of bladder fibrosis.
Immunofluorescence staining was conducted to assess the protein abundance of Piezo1 in fibroblasts from obstructed rat bladders. Bladder fibroblasts were cultured under normal atmospheric conditions (0 cmHO) or exposed to HHP (50 cmHO or 100 cmHO). Agonists or inhibitors of Piezo1, YAP1, and ROCK1 were used to determine the underlying mechanism.
The Piezo1 protein levels in fibroblasts from the obstructed bladder exhibited an elevation compared to the control group. HHP significantly promoted the expression of various pro-fibrotic factors and induced proliferation of fibroblasts. Additionally, the protein expression levels of Piezo1, YAP1, ROCK1 were elevated, and calcium influx was increased as the pressure increased. These effects were attenuated by the Piezo1 inhibitor Dooku1. The Piezo1 activator Yoda1 induced the expression of pro-fibrotic factors and the proliferation of fibroblasts, and elevated the protein levels of YAP1 and ROCK1 under normal atmospheric conditions in vitro. However, these effects could be partially inhibited by YAP1 or ROCK inhibitors.
The study suggests that HHP may exacerbate bladder fibrosis through activating Piezo1.
膀胱出口梗阻（BOO）在慢性阶段会导致显著的纤维化，并使膀胱压力升高。Piezo1 是一种机械敏感（MS）通道，可直接对机械刺激做出反应。为了寻找新的靶点来干预 BOO 引起的纤维化，本研究探讨了高静水压力（HHP）对 Piezo1 活性和膀胱纤维化进展的影响。
通过免疫荧光染色评估梗阻大鼠膀胱成纤维细胞中 Piezo1 的蛋白丰度。将膀胱成纤维细胞在正常大气压（0 cmHO）或 HHP（50 cmHO 或 100 cmHO）下培养。使用 Piezo1、YAP1 和 ROCK1 的激动剂或抑制剂来确定潜在的机制。
与对照组相比，梗阻膀胱成纤维细胞中的 Piezo1 蛋白水平升高。HHP 显著促进了各种促纤维化因子的表达，并诱导了成纤维细胞的增殖。此外，Piezo1、YAP1、ROCK1 的蛋白表达水平升高，随着压力的增加，钙内流增加。这些作用被 Piezo1 抑制剂 Dooku1 减弱。Piezo1 激动剂 Yoda1 在体外正常大气条件下诱导促纤维化因子的表达和成纤维细胞的增殖，并上调 YAP1 和 ROCK1 的蛋白水平。然而，YAP1 或 ROCK 抑制剂可部分抑制这些作用。
本研究表明，HHP 可能通过激活 Piezo1 加重膀胱纤维化。
