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大细胞SHP2缺乏通过抑制MAPK/NF-κB-依赖性炎症来缓解糖尿病病

Xue Han^1,2,3, Jiajia Wei¹, Ruyi Zheng¹

¹Zhejiang Provincial Key Laboratory of Laboratory Animals and Safety Research, Hangzhou Medical College, Hangzhou, China.

|February 23, 2024

概括

巨细胞Src同质性2-含有蛋白质氨酸酸酶2 (SHP2) 加快糖尿病病 (DN). 抑制巨细胞中的SHP2为治疗DN提供了潜在的治疗策略,减少功能障碍和纤维化.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
腎臟病學 (nephrology) 是一種醫學.

背景情况:

糖尿病病 (DN) 是糖尿病的一个主要并发症,主要是由慢性炎症驱动的.
确定关键的炎症点对于开发有效的DN治疗至关重要.

研究的目的:

在DN的背景下,研究Src同类2含蛋白氨酸酸酶2 (SHP2) 在巨细胞中的作用.
探索SHP2作为DN的潜在治疗点.

主要方法:

使用巨细胞特异性SHP2-knockout (SHP2-MKO) 小鼠和SHP2fl/fl小鼠接受了 estreptozotocin (STZ) 治疗.
在初级小鼠腹膜巨细胞 (MPM) 上进行RNA测序,以分析信号通路.
在糖尿病小鼠模型中使用药理学SHP2抑制剂SHP099.

主要成果:

在糖尿病患者和小鼠的巨细胞中,SHP2酸化被上调.
SHP2-MKO小鼠在STZ诱导的糖尿病中表现出减弱的功能障碍,纤维化和炎症.
删除SHP2影响了MPM中的MAPK和NF-κB信号通路和细胞因子释放.
在1型和2型糖尿病小鼠中,SHP099治疗保护了脏.

结论:

巨细胞SHP2在糖尿病病变的发病过程中起到加速作用.
准SHP2,特别是在巨细胞中,为DN管理提供了一个有希望的治疗途径.

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