功能基因组学揭示了脂肪-脏交叉作为通过OSM-OSMR途径导致纤维化的贡献者
Jing Zhang1,2, Zhaojun Liu2, Shihui Dong1
1National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210093, Jiangsu, China.
Functional & integrative genomics
|June 1, 2025
概括
糖尿病病风险与脂肪组织功能有关. 脂肪组织中的一种特定基因变异通过产生oncostatin-M来增加风险,这会在2型糖尿病中损害脏.
科学领域:
- 内分泌学 在内分泌学.
- 腎臟病學 (nephrology) 是一種醫學專業.
- 基因组学就是基因组学.
背景情况:
- 损伤是2型糖尿病的严重并发症,患者的病理生理学不同.
- 异常脂肪组织与损伤风险有关,但机制尚不清楚.
研究的目的:
- 研究糖尿病脏病 (DN) 中脂肪组织和脏损伤之间的关系.
- 探索脂肪功能基因组学和全基因组关联研究在理解DNA方面的作用.
主要方法:
- 集成的脂肪功能基因组学 (表观基因组,转录基因组,调节基因组) 与DNA的全基因组关联研究.
- 确定了一种特定的遗传风险变异 (rs2412980) 和其下游影响.
主要成果:
- 构建了脂肪组织的功能基因组学地图,突出显示了周围腺脂肪组织在脏疾病中的作用.
- 发现DN的遗传风险是通过脏和脂肪脏交叉介导的.
- 显示的风险变异rs2412980控制了脂肪组织中的OSM表达.
- 已证实脂肪衍生的 Kostatin-M (OSM) 重新编程纤维细胞,激活OSM-OSMR通路,与降低的eGFR,蛋白尿和肌素有关.
结论:
- 证实了脂肪组织和脏疾病之间的遗传联系.
- 通过OSM-OSMR途径揭示脂肪-轴促进糖尿病患者的纤维化.
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