细胞外纤维细胞特异蛋白1通过核因素红色素2相关因子介导的抗氧化活性产生保护作用
Naoki Takahashi1, Seiji Yokoi1, Hideki Kimura2
1Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-Cho, Yoshida-Gun, Fukui, 910-1193, Japan.
Scientific reports
|December 18, 2023
概括
由细胞分泌的纤维细胞特异蛋白1 (FSP1) 保护管免受损伤. 这种保护作用通过激活Nrf2通路来调节,减少氧化应激和细胞死亡.
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:
- 足细胞损伤与各种类型的淋巴细胞神经炎有关.
- 纤维细胞特异蛋白1 (FSP1) 被细胞外分泌,影响远处的细胞.
- 细胞分泌的FSP1在管中的作用以前未被探索.
研究的目的:
- 为了研究 podocyte 分泌的 FSP1 对管细胞的影响.
- 阐明FSP1-介导保护的基础分子机制.
- 在急性损伤模型中评估FSP1的治疗潜力.
主要方法:
- 在管状上皮细胞系 (mProx) 中进行RNA微阵列分析.
- 对Nrf2激活,核转位,谷氨水平和反应性氧物种 (ROS) 生产的测试.
- 在体内研究中,使用西斯的腎毒性小鼠模型和具有 podocyte 特定 FSP1 表达的转基因小鼠.
主要成果:
- 在mProx细胞中与Nrf2激活相关的FSP1上调基因.
- FSP1促进了Nrf2核转位,增加了谷氨,抑制了ROS的产生,并减少了西斯胺诱导的细胞死亡.
- 在思普拉丁毒性小鼠模型中,FSP1改善了急性管管损伤.
结论:
- 由细胞分泌的细胞外FSP1通过Nrf2-介导的抗氧化活性对管状细胞产生保护作用.
- 细胞和管状上皮细胞之间存在一个远程通信网络,以限制损伤.
- 来自细胞的FSP1代表了脏疾病的潜在治疗标.
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