期刊
JOURNAL OF EXTRACELLULAR VESICLES
卷 11, 期 3, 页码 -出版社
WILEY
DOI: 10.1002/jev2.12203
关键词
CD44; exosomes; OPN; renal fibrosis; beta-catenin
类别
资金
- National Key R&D Program of China [2020YFC2005000]
- National Natural Science Foundation of China [82070707, 91949114, 81900627, 82000652]
- Chinese Postdoctoral Science Foundation [2020T130277]
- Guangxi Natural Science Foundation [2021JJA140160]
- Guangxi Administration of Traditional Chinese Medicine [GZZC2019107]
- Chinese and Western Medicine [2019KCXTD014]
- Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110105004]
- Outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110102004]
- Outstanding youth cultivation program in Nanfang Hospital [2021J001]
The activation of beta-catenin in renal tubular cells leads to the release of exosomes containing osteopontin (OPN) that are then taken up by fibroblasts, promoting their proliferation and activation through binding with CD44. Deletion of beta-catenin or CD44 greatly improves renal fibrosis. N-terminal fragment of OPN is secreted into the urine and negatively correlated with kidney function in CKD patients. Urinary exosomes from CKD patients accelerate renal fibrosis, which can be blocked by CD44 deletion.
Tubular injury and peripheral fibroblast activation are the hallmarks of chronic kidney disease (CKD), suggesting intimate communication between the two types of cells. However, the underlying mechanisms remain to be determined. Exosomes play a role in shuttling proteins and other materials to recipient cells. In our study, we found that exosomes were aroused by beta-catenin in renal tubular cells. Osteopontin (OPN), especially its N-terminal fragment (N-OPN), was encapsulated in beta-catenin-controlled tubular cell-derived exosome cargo, and subsequently passed to fibroblasts. Through binding with CD44, exosomal OPN promoted fibroblast proliferation and activation. Gene deletion of beta-catenin in tubular cells (Ksp-beta-catenin(-/-)) or gene ablation of CD44 (CD44(-/-)) greatly ameliorated renal fibrosis. Notably, N-OPN was carried by exosome and secreted into the urine of patients with CKD, and negatively correlated with kidney function. The urinary exosomes from patients with CKD greatly accelerated renal fibrosis, which was blocked by CD44 deletion. These results suggest that exosome-mediated activation of the OPN/CD44 axis plays a key role in renal fibrosis, which is controlled by beta-catenin.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据