Retinoic Acid in Myofibrolast Activation and Kidney Fibrosis

视黄酸在肌纤维细胞激活和肾纤维化中的作用

基本信息

批准号：
8766897
负责人：
BENJAMIN D. HUMPHREYS
金额：
$ 24.32万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-07 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8766897
关键词：
Acute Renal Failure with Renal Papillary Necrosis Address Adult Adverse effects Agreement Binding Cells Chronic Chronic Kidney Failure Cicatrix Clinic Complex Data Development Dominant-Negative Mutation Dose End stage renal failure Enzymes Experimental Models Extracellular Matrix Feedback Fibroblasts Fibrosis Foundations Gene Targeting Genes Genetic Health Human In Vitro Injury Kidney Kidney Diseases Kidney Failure Lead Ligand Binding Literature Mediating Metabolism Modeling Mus Myofibroblast Organ Pathway interactions Patients Pattern Pericytes Pharmaceutical Preparations Production Publishing Rattus Receptor Signaling Renal function Reporter Retinaldehyde Retinoic Acid Receptor Retinoids Signal Transduction Site Solid Techniques Testing Therapeutic Tissues Toxic effect Translations Tretinoin United States Up-Regulation Vitamin A Work base cell type improved in vitro Model in vivo inhibitor/antagonist injured interstitial kidney cell kidney cortex novel prevent progenitor public health relevance retinaldehyde dehydrogenase small molecule treatment strategy

项目摘要

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.

描述（申请人提供）：肾脏纤维化是所有慢性肾脏疾病的最终共同途径，但美国尚无批准治疗肾脏纤维化的药物。人们普遍认为，肌成纤维细胞是导致纤维化肾病疤痕形成的细胞类型，消除这些细胞可以改善实验模型中的肾功能。然而，关于可能改变肌成纤维细胞功能和减少疤痕的小分子的信息非常少。在这里，我们建议剖析视黄酸及其前体改善肾纤维化的能力，作为建立新治疗范例的基础。我们的初步数据表明类维生素A抑制肌成纤维细胞功能，我们将使用体外和体内补充策略验证这一观察结果。生成的数据将为通过靶向肌成纤维细胞中的视黄酸信号传导来预防肾纤维化的新疗法的转化建立明确的途径。