Slowing polycystic kidney disease by inhibition of HIF-1α-dependent- and calcium-mediated secretory signaling pathways (A02)

通过抑制 HIF-1α 依赖性和钙介导的分泌信号通路减缓多囊肾病 (A02)

• 批准号: 415807670
• 金额: --
• 依托单位: Medizinische Klinik 4 - Nephrologie und Hypertensiologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/415807670?language=en
• 关键词: Slowing; polycystic; kidney; disease; inhibition

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by continuous cyst growth due to fluid secretion into the cyst lumen. Our preliminary work indicates that ATP-dependent, Ca2+-activated Cl- secretion as well as HIF-1α and ROS signaling contribute to this fluid transport. Here, we will test if cyst progression can be slowed down by pharmacological inhibition of these pathways. In addition, we will analyze the mechanism leading to luminal ATP release and its effect on cyst enlargement. The expected results will help to understand the underlying mechanisms of continuous cyst expansion in ADPKD and to identify applicable drug targets to inhibit cyst growth and preserve renal function.

常染色体显性遗传性多囊肾病(ADPKD)的特点是囊腔内液体分泌导致囊腔持续生长。我们的初步工作表明，依赖于三磷酸腺苷、钙激活的氯离子分泌以及缺氧诱导因子-1的α和ROS信号参与了这种液体的运输。在这里，我们将测试是否可以通过药物抑制这些途径来减缓囊性病变的进展。此外，我们还将分析导致腔内ATP释放的机制及其对囊肿胀大的影响。预期的结果将有助于了解ADPKD持续囊性扩张的潜在机制，并确定适用的药物靶点，以抑制囊性生长和保护肾功能。