Retinoic Acid in Myofibrolast Activation and Kidney Fibrosis

描述（由申请人提供）：肾纤维化是所有慢性肾脏疾病的最终共同途径，但在美国没有批准的治疗肾纤维化的药物。普遍认为肌成纤维细胞是纤维化肾病中负责瘢痕形成的细胞类型，并且消融这些细胞在实验模型中改善了肾功能。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，我们建议解剖视黄酸及其前体改善肾纤维化的能力，作为建立一个新的治疗模式的基础。我们的初步数据表明，类维生素A抑制肌成纤维细胞的功能，我们将验证这一观察使用互补的策略在体外和体内。所产生的数据将建立一个明确的路径，以翻译一种新的疗法，以防止肾纤维化，通过靶向视黄酸信号在肌成纤维细胞。

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.