通过m6A甲基化对RNF183的修饰通过调节PKM2的Ubiquitination和降解来调节糖尿病病中的Podocyte功能障碍
Dongwei Guo1,2,3, Yingxue Pang1,2,3, Wenjie Wang1,2,3
1Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China.
Cells
|March 12, 2025
概括
在糖尿病病中,RNF183蛋白水平下降,导致细胞损伤. 恢复RNF183,可能通过m6A甲基化,可能为糖尿病损伤提供新的治疗策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 糖尿病病 (DKD) 是一种主要的糖尿病并发症,由 podocyte 功能障碍驱动.
- 环指蛋白183 (RNF183),一种E3结合酶,在DKD病变发生过程中没有明确的作用.
- 了解RNF183在细胞中的功能对于DKD治疗至关重要.
研究的目的:
- 研究RNF183在糖尿病病 (DKD) 中的作用.
- 探索RNF183表达在细胞中的调节机制.
- 确定RNF183是否可以成为DKD的治疗点.
主要方法:
- 在人类和小鼠脏组织和培养的细胞中进行转录组测序和基因表达分析.
- N6-甲基氨酸 (m6A) RNA甲基化分析,包括去甲基酶抑制剂治疗.
- 共同免疫沉 (Co-IP) 和液体染色学-质谱学 (LC-MS) 以确定蛋白质相互作用.
- 评估细胞亡,自和细胞标记物表达.
主要成果:
- 在DKD患者,糖尿病小鼠和高葡萄糖治疗的 podocytes 中,RNF183 的表达显著降低.
- 降低RNF183的调节会损害自,增加细胞亡,并减少细胞细胞中的细胞标记物.
- 通过m6A甲基化调节RNF183,其中METTL3和IGF2BP2参与其转录.
- RNF183直接在PKM2上无处不在,促进其降解,并减轻高葡萄糖诱导的细胞损伤.
结论:
- 在DKD中,RNF183的表达是下调的,通过减少PKM2的无化,有助于细胞损伤.
- 在高葡萄糖条件下,m6A甲基化是RNF183表达的关键调节者.
- 在糖尿病病中,RNF183代表了一种潜在的治疗点,可以缓解糖尿病病中细胞损伤.
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