Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, Florida, USA.
J Clin Invest. 2021 May 17;131(10). doi: 10.1172/JCI149043.
Kidney diseases affect more than 15% of adults in the US, yet drug development in the kidney field, when compared with that for other common diseases, has been lagging behind. Modifiers that increase the susceptibility to injury and contribute to the pathogenesis and progression of kidney disease include genetic and environmental factors and epigenetic mechanisms. In this issue of the JCI, Cao et al. and Doke et al. independently report the identification of a susceptibility factor called Dachshund homolog 1 (DACH1). Both groups identify an association of reduced DACH1 expression with kidney disease, using different screening approaches, studying different types of human kidney diseases, and using different experimental models, making the fact that both stumbled over the same protein very compelling. Combined, these studies highlight DACH1 as a key safeguard in the kidney, granting various cell types proper function by modulating several molecular pathways.
肾脏疾病影响着美国超过 15%的成年人，然而与其他常见疾病相比，肾脏领域的药物研发一直滞后。增加肾脏损伤易感性并导致肾脏疾病发病机制和进展的修饰因子包括遗传和环境因素以及表观遗传机制。在本期 JCI 中，Cao 等人和 Doke 等人独立报道了一种名为 Dachshund 同源物 1（DACH1）的易感性因子的鉴定。这两个小组都使用不同的筛选方法、研究不同类型的人类肾脏疾病和使用不同的实验模型，发现 DACH1 表达降低与肾脏疾病相关，从而独立鉴定出 DACH1 表达降低与肾脏疾病之间的关联，这一事实非常令人信服。这些研究结合在一起，突出了 DACH1 作为肾脏的关键保护因子的作用，通过调节多个分子途径赋予各种细胞类型适当的功能。
