与G蛋白结合受体107的缺乏促进了糖尿病病的发展
Deping Xu1,2, Ziwen Tong1, Ping Yang1
1Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, China.
Molecular biomedicine
|February 11, 2025
概括
G蛋白结合受体107 (GPR107) 缺陷通过降低细胞中的IV型原蛋白 (COL4) 清除而加剧糖尿病病 (DN). 恢复GPR107功能可能为DN提供一种新的治疗策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 糖尿病病 (DN) 的特点是由于细胞外细胞基质 (ECM) 中的第四类原 (COL4) 积累而导致球底膜 (GBM) 变厚.
- 足细胞内细胞结核是维护GBM完整性和COL4平衡至关重要的.
- 众所周知,G蛋白结合受体107 (GPR107) 可以调节克拉斯林依赖性内细胞分裂.
研究的目的:
- 为了研究GPR107在调节 podocyte ECM 中 COL4 平衡中的作用.
- 探索GPR107作为DN的潜在治疗点.
主要方法:
- 评估了DN患者和链毒素 (STZ) 诱导的DN小鼠的组织中的GPR107表达.
- 在高葡萄糖条件下使用了缺乏GPR107的小鼠和体外 podocyte 模型.
- 研究了涉及类型1 (AT1R) 血管新素II受体和下游信号通路的氨酸介导内细胞结核 (CME) 的机制.
主要成果:
- 在DN患者的脏和STZ诱导的DN小鼠中,GPR107的表达显著减少.
- 在STZ诱导的DN小鼠中,GPR107缺乏症加剧了损伤,GBM加厚和COL4积累增加.
- 在体外,GPR107缺乏导致通过增加产量和降低降解来积累COL4,与AT1R内部化和AT1R/Ca2+/CREB通路激活受损有关,最终上调COL4合成和下调MMP-2.
结论:
- 通过调节AT1R内细胞分裂,GPR107在细胞中维持COL4稳态起着至关重要的作用.
- 由于GPR107缺乏,通过增强的COL4合成和降低降解,有助于DN病原性.
- GPR107是缓解DN进展的有希望的治疗标.
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