Retinoic Acid in Myofibrolast Activation and Kidney Fibrosis

描述(申请人提供)：肾纤维化是所有慢性肾脏疾病的最终共同途径，但在美国还没有被批准的治疗肾纤维化的药物。人们普遍认为，肌成纤维细胞是导致纤维化肾脏疾病瘢痕形成的细胞类型，在实验模型中，切除这些细胞可以改善肾功能。然而，关于可能改变肌成纤维细胞功能和减少瘢痕的小分子的信息很少。在这里，我们建议剖析维甲酸及其前体改善肾脏纤维化的能力，作为建立新的治疗范例的基础。我们的初步数据表明，维甲酸类化合物抑制肌成纤维细胞的功能，我们将在体外和体内使用互补策略验证这一观察结果。产生的数据将建立一条明确的途径，通过靶向肌成纤维细胞中的维甲酸信号来翻译一种预防肾脏纤维化的新疗法。

DESCRIPTION (provided by applicant): Kidney fibrosis is the final common pathway of all chronic kidney diseases but there is no approved drug to treat kidney fibrosis in the United States. There is general agreement that myofibroblasts are the cell type responsible for scar formation in fibrotic kidney disease, and ablating these cells improves kidney function in experimental models. However, there is very little information regarding small molecules that might alter myofibroblast function and reduce scar. Here we propose to dissect the ability of retinoic acid and its precursors to ameliorate kidney fibrosis as a foundation for establishing a new treatment paradigm. Our preliminary data indicates that retinoids inhibit myofibroblast function, and we will validate this observation using complementary strategies in vitro and in vivo. The data generated will establish a clear path towards translation of a new therapy to prevent kidney fibrosis by targeting retinoic acid signaling in myofibroblasts.