Academic Journal

Proton pump inhibitors enhance macropinocytosis‐mediated extracellular vesicle endocytosis by inducing membrane v‐ATPase assembly

التفاصيل البيبلوغرافية
العنوان: Proton pump inhibitors enhance macropinocytosis‐mediated extracellular vesicle endocytosis by inducing membrane v‐ATPase assembly
المؤلفون: Xinliang Lu, Zhengbo Song, Jiayue Hao, Xianghui Kong, Weiyi Yuan, Yingying Shen, Chengyan Zhang, Jie Yang, Pengfei Yu, Yun Qian, Gensheng Zhang, Huajun Feng, Jianli Wang, Zhenzhai Cai, Zhijian Cai
المصدر: Journal of Extracellular Vesicles, Vol 13, Iss 4, Pp n/a-n/a (2024)
بيانات النشر: Wiley, 2024.
سنة النشر: 2024
المجموعة: LCC:Cytology
مصطلحات موضوعية: extracellular vesicles, macropinocytosis, pH, proton pump inhibitors, v‐ATPases, Cytology, QH573-671
الوصف: Abstract Besides participating in diverse pathological and physiological processes, extracellular vesicles (EVs) are also excellent drug‐delivery vehicles. However, clinical drugs modulating EV levels are still lacking. Here, we show that proton pump inhibitors (PPIs) reduce EVs by enhancing macropinocytosis‐mediated EV uptake. PPIs accelerate intestinal cell endocytosis of autocrine immunosuppressive EVs through macropinocytosis, thereby aggravating inflammatory bowel disease. PPI‐induced macropinocytosis facilitates the clearance of immunosuppressive EVs from tumour cells, improving antitumor immunity. PPI‐induced macropinocytosis also increases doxorubicin and antisense oligonucleotides of microRNA‐155 delivery efficiency by EVs, leading to enhanced therapeutic effects of drug‐loaded EVs on tumours and acute liver failure. Mechanistically, PPIs reduce cytosolic pH, promote ATP6V1A (v‐ATPase subunit) disassembly from the vacuolar membrane and enhance the assembly of plasma membrane v‐ATPases, thereby inducing macropinocytosis. Altogether, our results reveal a mechanism for macropinocytic regulation and PPIs as potential modulators of EV levels, thus regulating their functions.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2001-3078
Relation: https://doaj.org/toc/2001-3078
DOI: 10.1002/jev2.12426
URL الوصول: https://doaj.org/article/2ee6302e41d34ca888ec5d6760bcbf64
رقم الانضمام: edsdoj.2ee6302e41d34ca888ec5d6760bcbf64
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20013078
DOI:10.1002/jev2.12426