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富血小板血浆通过AKT/Rab27途径促进间充质干细胞外泌体旁分泌以修复急性肾损伤。

Platelet-rich plasma promotes MSCs exosomes paracrine to repair acute kidney injury via AKT/Rab27 pathway.

作者信息

Ji Cheng, Zhang Jiahui, Zhou Zixuan, Shi Hui, Liu Wanzhu, Sun Fengtian, Zhang Chenxiao, Zhang Leilei, Sun Zixuan, Qian Hui

机构信息

Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.

Department of Emergency, The Affiliated People's Hospital of Jiangsu University Zhenjiang 212002, China.

出版信息

Am J Transl Res. 2021 Mar 15;13(3):1445-1457. eCollection 2021.

Abstract

Acute kidney injury (AKI) is defined by rapid deterioration of renal function, and is a common complication in hospitalized patients. Among the recent therapeutic options, mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for damaged tissue repair. Platelet rich plasma (PRP) regulates mesenchymal cells to repair tissue damage through the release of growth factors. In this study, we proposed a possible therapeutic use of MSCs stimulated by platelet-rich plasma (PRP-MSCs) in a glycerin-induced AKI murine model. and studies, showed that PRP-MSCs could significantly attenuate serum blood urea nitrogen and creatinine levels, and reverse the histopathological kidney damage. PRP-MSCs treatment reduced renal tubular cell apoptosis stimulated by glycerin. We confirmed that PRP promoted the proliferation and reinforced the stemness of MSCs by inducing YAP nucleus expression, and that PRP promoted MSCs exosomes in a paracrine manner to repair AKI through an activated AKT/Rab27 pathway. Our results revealed that the PRP stimulated MSCs paracrine pathway could effectively alleviate glycerin-induced AKI. Therefore, PRP pretreatment may be a new method to improve the therapeutic effect of MSCs.

摘要

急性肾损伤(AKI)定义为肾功能迅速恶化,是住院患者的常见并发症。在最近的治疗选择中,间充质干细胞(MSCs)被认为是受损组织修复的一种有前景的治疗策略。富血小板血浆(PRP)通过释放生长因子调节间充质细胞以修复组织损伤。在本研究中,我们提出了富血小板血浆刺激的间充质干细胞(PRP-MSCs)在甘油诱导的AKI小鼠模型中的一种可能的治疗用途。 和 研究表明,PRP-MSCs可显著降低血清血尿素氮和肌酐水平,并逆转肾脏组织病理学损伤。PRP-MSCs治疗减少了甘油刺激的肾小管细胞凋亡。我们证实,PRP通过诱导YAP核表达促进MSCs增殖并增强其干性,并且PRP以旁分泌方式促进MSCs外泌体通过激活的AKT/Rab27途径修复AKI。我们的结果表明,PRP刺激的MSCs旁分泌途径可有效减轻甘油诱导的AKI。因此,PRP预处理可能是提高MSCs治疗效果的一种新方法。

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