Delivery of exogenous miR-19b by Wharton's Jelly Mesenchymal Stem Cells attenuates transplanted kidney ischemia/reperfusion injury by regulating cellular metabolism.

IF 5.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Drug Delivery and Translational Research Pub Date : 2025-03-01 Epub Date: 2024-06-25 DOI:10.1007/s13346-024-01645-3

Xiaoqiang Wu, Xuan Wu, Zhiwei Wang, Xiangyong Tian, Chan Zhang, Guanghui Cao, Yue Gu, Tianzhong Yan

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Abstract

Renal ischemia-reperfusion injury (IRI) frequently occurs following kidney transplantation, and exosomes derived from umbilical cord mesenchymal stem cells (WJ-MSC-Exos) have shown promise in treating IRI in transplanted kidneys. Our study delved into the potential mechanism of WJ-MSC-Exos in ameliorating IRI in transplanted kidneys, revealing that miR-19b is abundantly present in WJ-MSC-Exos. Both in vivo and in vitro experiments demonstrated that the absence of miR-19b abolished the protective effects of WJ-MSC-Exos against renal IRI. Mechanistically, miR-19b suppressed glycogen synthase kinase-3β (GSK3β) expression, thereby stabilizing PDXK protein through direct binding. Treatment with WJ-MSC-Exos led to reduced PDXK levels and enhanced pyridoxine accumulation, ultimately mitigating IRI in transplanted kidneys and I/R-induced HK2 cell apoptosis. These findings elucidate the underlying mechanism of WJ-MSC-Exos in alleviating IRI in transplanted kidneys, unveiling novel therapeutic targets for post-kidney transplantation IRI and providing a solid theoretical foundation for the clinical application of WJ-MSC-Exos in IRI treatment post-transplantation.

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沃顿果冻间充质干细胞输送外源 miR-19b 可通过调节细胞代谢减轻移植肾缺血再灌注损伤。

肾移植后经常会发生肾缺血再灌注损伤（IRI），而从脐带间充质干细胞（WJ-MSC-Exos）中提取的外泌体有望治疗移植肾的IRI。我们的研究深入探讨了WJ-间充质干细胞外泌体改善移植肾IRI的潜在机制，揭示了miR-19b大量存在于WJ-间充质干细胞外泌体中。体内和体外实验均表明，miR-19b的缺失会削弱WJ-间充质干细胞-Exos对肾脏IRI的保护作用。从机制上讲，miR-19b抑制了糖原合酶激酶-3β（GSK3β）的表达，从而通过直接结合稳定了PDXK蛋白。用WJ-间充质干细胞-Exos处理后，PDXK水平降低，吡哆醇积累增加，最终减轻了移植肾的IRI和I/R诱导的HK2细胞凋亡。这些发现阐明了WJ-间充质干细胞-Exos缓解移植肾IRI的内在机制，揭示了肾移植后IRI的新型治疗靶点，为WJ-间充质干细胞-Exos在移植后IRI治疗中的临床应用提供了坚实的理论基础。

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来源期刊

Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY

CiteScore

11.70

自引率

1.90%

发文量

160

期刊介绍： The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.