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神经生长因子的合成和分泌由膀细胞中的氧化在高血糖环境下在体外受调节
Stephanie Sirmakesyan1, Aya Hajj1, Aalya Hamouda1
1Lady Davis Institute for Medical Research, Montreal, Quebec, Canada.
Nitric oxide : biology and chemistry
|September 12, 2023
概括
高葡萄糖会增加氧化 (NO),从而降低膀细胞中的神经生长因子 (NGF). 这种NO诱导的NGF下降涉及光滑肌肉和尿细胞的特定途径,可能解释代谢综合征中的过度活性膀 (OAB).
科学领域:
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 细胞生物学 细胞生物学
- 代谢综合征研究 代谢综合征研究
背景情况:
- 过度活跃的膀 (OAB) 与患者尿液中的神经生长因子 (NGF) 低,氧化 (NO) 高相关.
- 超血糖,模仿代谢综合征,可能会影响膀细胞中的NO和NGF水平.
研究的目的:
- 研究氧化 (NO) 对大鼠膀光滑肌肉 (SMC) 和尿道细胞 (URO) 神经生长因子 (NGF) 合成的调节作用.
- 阐明在OAB中观察到的NO和NGF之间的反向关系背后的细胞机制.
主要方法:
- 主要大鼠膀SMC和URO是在高血糖条件下培养的.
- 使用NO合成酶抑制剂 (l-NAME) 和NO供体 (SNP) 来调节氧化 (NO) 的生成.
- 评估了NGF水平,mRNA表达,循环GMP (cGMP) 含量和矩阵金属蛋白酶 (MMP) 活性 (MMP-7,MMP-9). 在MMP-9淘汰赛研究中使用了CRISPR-Cas9.
主要成果:
- 高血糖症增加了NO和减少了NGF分泌在UROs和SMCs,除了当NO合成被抑制.
- 在UROs中,NO诱导的NGF减少依赖于MMP-9,而MMP-7活性增加.
- 在SMC中,NO通过cGMP依赖的途径降低了NGF分泌,并降低了MMP-7活性,影响了proNGF转化.
结论:
- 由高血糖症引发的增强的NO分泌,通过涉及cGMP和MMPs (MMP-7和MMP-9) 的独特细胞特异性途径减少NGF分泌.
- 这些发现为在代谢综合征的OAB患者中观察到的低NGF和高NO的细胞基础.
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