Androgen-regulated microRNAs as relevant effectors of adipogenesis inhibition

雄激素调节的 microRNA 作为脂肪生成抑制的相关效应子

• 批准号: 404369685
• 负责人: Dr. Thomas Greither
• 金额: --
• 依托单位: Institut für Molekulare Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/404369685?language=en
• 关键词: Androgen; regulated; microRNAs; relevant; effectors

Late-onset hypogonadism (LOH) as well as its associated symptoms like an increased prevalence for the development of a metabolic syndrome, type 2 diabetes and cardiovascular diseases will play an important role in the public health system of the future decades considering the progressing demographic ageing of western societies.Aim of the analyses underlying this proposal is the evaluation of potential signaling pathways favoring adipocytic differentiation and a decreased insulin sensitivity due to lowered androgen serum levels and though that causally influencing the negative after-effects of LOH. In this context the interaction between androgens, microRNAs like miR-375 and further androgen-regulated microRNAs and several molecular factors essential for adipocytic differentiation like CEBPalpha, PPARgamma, leptin and adiponectin as well as their receptors will be studied in-vitro in a preadipocytic cell model (SGBS) and functionally and mechanistically described. Additionally, the analyses of potential novel therapeutics (selective androgen receptor modulators - SARMs) of LOH will build a bridge between basic research-related in-vitro studies and the clinical praxis.

考虑到西方社会日益老龄化的人口结构，晚发性性腺功能减退症(LOH)及其相关症状，如代谢综合征、2型糖尿病和心血管疾病的发病率增加，将在未来几十年的公共卫生系统中发挥重要作用。支持这一建议的分析目的是评估有利于脂肪细胞分化的潜在信号通路，以及由于雄激素血清水平降低而导致的胰岛素敏感性降低，尽管这会因果地影响LOH的负面后遗症。在此背景下，雄激素、microRNAs(如miR-375)和雄激素调控的microRNAs与几种脂肪细胞分化所必需的分子因子如CEBPalpha、PPARGamma、Leptin和Adiponectin及其受体之间的相互作用将在体外脂肪细胞前细胞模型(SGBs)中进行研究，并从功能和机制上进行描述。此外，对潜在的新疗法(选择性雄激素受体调节剂-SARM)的分析将在基础研究相关的体外研究和临床实践之间架起一座桥梁。

项目成果

MiR-130a in the adipogenesis of human SGBS preadipocytes and its susceptibility to androgen regulation

• DOI: 10.1080/21623945.2020.1750256
• 发表时间: 2020-01-01
• 期刊: ADIPOCYTE
• 影响因子: 3.3
• 作者: Greither, Thomas;Wenzel, Carina;Behre, Hermann M.
• 通讯作者: Behre, Hermann M.