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Bone marrow mesenchymal stem cell-derived exosomal miR-34c-5p ameliorates RIF by inhibiting the core fucosylation of multiple proteins
Molecular Therapy ( IF 12.1 ) Pub Date : 2021-10-19 , DOI: 10.1016/j.ymthe.2021.10.012
Xuemei Hu 1 , Nan Shen 2 , Anqi Liu 1 , Weidong Wang 2 , Lihua Zhang 3 , Zhigang Sui 3 , Qingzhu Tang 2 , Xiangning Du 2 , Ning Yang 2 , Wantao Ying 4 , Biaojie Qin 2 , Zhitong Li 1 , Lin Li 1 , Nan Wang 2 , Hongli Lin 2
Affiliation  

Renal interstitial fibrosis (RIF) is an incurable pathological lesion in chronic kidney diseases. Pericyte activation is the major pathological characteristic of RIF. Fibroblast and macrophage activation are also involved in RIF. Studies have revealed that core fucosylation (CF), an important post-translational modification of proteins, plays a key role in pericyte activation and RIF by regulating multiple profibrotic signaling pathways as a hub-like target. Here, we reveal that mesenchymal stem cell (MSC)-derived exosomes reside specifically in the injured kidney and deliver microRNA (miR)-34c-5p to reduce cellular activation and RIF by inhibiting CF. Furthermore, we showed that the CD81-epidermal growth factor receptor (EGFR) ligand-receptor complex aids the entry of exosomal miR-34c-5p into pericytes, fibroblasts, and macrophages. Altogether, our findings reveal a novel role of MSC-derived exosomes in inhibiting multicellular activation via CF and provide a potential intervention strategy for renal fibrosis.



中文翻译:

骨髓间充质干细胞来源的外泌体 miR-34c-5p 通过抑制多种蛋白质的核心岩藻糖基化来改善 RIF

肾间质纤维化(RIF)是慢性肾脏病中无法治愈的病理病变。周细胞活化是RIF的主要病理特征。成纤维细胞和巨噬细胞的激活也参与 RIF。研究表明,核心岩藻糖基化 (CF) 是一种重要的蛋白质翻译后修饰,通过作为中枢样靶点调节多个促纤维化信号通路,在周细胞激活和 RIF 中发挥关键作用。在这里,我们发现间充质干细胞 (MSC) 衍生的外泌体特异性存在于受伤的肾脏中,并传递 microRNA (miR)-34c-5p 以通过抑制 CF 来减少细胞活化和 RIF。此外,我们发现 CD81-表皮生长因子受体 (EGFR) 配体-受体复合物有助于外泌体 miR-34c-5p 进入周细胞、成纤维细胞和巨噬细胞。共,

更新日期:2021-10-19
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