蛋白酶激活受体1-中介性损伤的podocytes在糖尿病病症
Ruslan Bohovyk1, Sherif Khedr2, Vladislav Levchenko1
1Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL.
Diabetes
|September 18, 2023
概括
糖尿病脏病 (DN) 中血清蛋白酶的升高过度激活蛋白酶激活受体1 (PAR1) 信号. 这一途径通过TRPC6道增加细胞内,导致细胞损伤和病进展.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 糖尿病学 糖尿病学
- 分子生物学分子生物学
背景情况:
- 尿中血清蛋白酶的增加与糖尿病病 (DN) 的严重程度相关.
- 血清蛋白酶可能会通过蛋白酶激活受体 (PAR) 影响 podocyte ([Ca2+]i) 动态.
研究的目的:
- 研究PAR1介导信号在DN中的作用.
- 阐明DN中连接蛋白酶,流入和细胞损伤的机制.
主要方法:
- 使用培养的人类 podocytes 和老鼠模型 (Goto-Kakizaki,T2DN, PAR1 淘汰赛).
- 采用成像,西斑,扫描离子导电显微镜和补丁分析.
- 在T2DN大鼠和T2DNPar1+/-大鼠中评估了淋巴细胞损伤和血栓激素水平.
主要成果:
- PAR1的激活通过受体细胞中的TRPC6通道增加了细胞内 ([Ca2+]i).
- 在高葡萄糖和T2DN大鼠 podocytes 下的人类 podocytes 显示高 PAR1-介导的 [Ca2+]i.
- 在T2DN大鼠中,血栓激素水平较高;在T2DNPar1+/-大鼠中,球损伤减少.
结论:
- 在DN中血清蛋白酶的升高通过PAR1-TRPC6信号传递在受体细胞中促进了过度[Ca2+]i流入.
- 这种信号通路有助于细胞的亡,白蛋白尿和淋巴细胞损伤.
- 向血清蛋白酶或PAR通路可能为DN提供治疗策略.
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