皮质DPP4通过向氨酸- ангиотензин系统中的ACE2活性来促进Ang II驱动的纤维化
Yingying Zhang1, Ruizhi Tan2, Lehao Wu1
1Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
International journal of biological sciences
|July 3, 2025
概括
双基酸酶-IV (DPP4) 抑制通过恢复素-血管新生素系统 (RAS) 抗纤维性通路来改善纤维化. 向表皮DPP4为慢性病 (CKD) 的进展提供了一种新的治疗策略.
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
- 药理学 药理学是指药理学的学科.
背景情况:
- 纤维化驱动慢性病 (CKD) 进展到末期病 (ESRD).
- 宁-血管素系统 (RAS) 在病理学中起着至关重要的作用.
- 皮质二基酸酶-IV (DPP4) 水平与CKD进展相关.
研究的目的:
- 研究表皮DPP4在纤维化中的作用.
- 阐明DPP4影响RAS的分子机制.
- 评估DPP4抑制作为CKD的治疗策略.
主要方法:
- 使用单边尿路阻塞 (UUO) 和缺血/反 (I/R) 损伤模型 in vivo.
- 用人上皮HK-2细胞在体外用 ангиотензинII (AngII) 刺激.
- 用linagliptin进行脏特异性DPP4和向DPP4的删除.
主要成果:
- 在受伤的脏和Ang II刺激细胞中,DPP4的调节升高.
- 特异性DPP4删除改善了UUO和I/R诱导的纤维化.
- DPP4直接与ACE2结合,抑制Ang{1-7) /MasR轴,并诱导AT1R轴.
- 利纳吉普丁治疗恢复了抗纤维性RAS通路,并在I / R受伤的脏中阻断了纤维化.
结论:
- 表皮DPP4作为Ang{1-7) /MasR轴的新型抑制剂和AT1R轴的诱导剂.
- 用linagliptin针对DPP4有效地阻断了纤维化进展.
- 表皮DPP4是增强RAS抗纤维性活性在CKD中的潜在治疗点.
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