Microvesicles from Mesenchymal Stem Cells Overexpressing MiR-34a Ameliorate Renal Fibrosis In Vivo.

IF 0.8 4区医学 Q4 UROLOGY & NEPHROLOGY

Iranian journal of kidney diseases Pub Date : 2024-04-25 DOI:10.5254/s9bdqs74

Yan Wang, Ping Hu, Yangping Li, Ruijuan Dong, Juan He

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引用次数: 0

Abstract

We recently discovered that microvesicles (MVs) derived from mesenchymal stem cells (MSCs) overexpressing miRNA-34a can alleviate experimental kidney injury in mice. In this study, we further explored the effects of miR34a-MV on renal fibrosis in the unilateral ureteral obstruction (UUO) models. Methods. Bone marrow MSCs were modified by lentiviruses overexpressing miR-34a, and MVs were collected from the supernatants of MSCs. C57BL6/J mice were divided into control, unilateral ureteral obstruction (UUO), UUO + MV, UUO + miR-34aMV and UUO + miR-34a-inhibitor-MV groups. MVs were injected to mice after surgery. The mice were then euthanized on day 7 and 14 of modeling, and renal tissues were collected for further analyses by Hematoxylin and eosin, Masson's trichrome, and Immunohistochemical (IHC) staining. Results. The UUO + MV group exhibited a significantly reduced degree of renal interstitial fibrosis with inflammatory cell infiltration, tubular epithelial cell atrophy, and vacuole degeneration compared with the UUO group. Surprisingly, overexpressing miR-34a enhanced these effects of MSC-MV on the UUO mice. Conclusion. Our study demonstrates that miR34a further enhances the effects of MSC-MV on renal fibrosis in mice through the regulation of epithelial-to-mesenchymal transition (EMT) and Notch pathway. miR-34a may be a candidate molecular therapeutic target for the treatment of renal fibrosis. DOI: 10.52547/ijkd.7673.

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过表达 MiR-34a 的间充质干细胞微囊可改善体内肾脏纤维化

我们最近发现，间充质干细胞（MSCs）过度表达 miRNA-34a 后产生的微囊泡（MVs）可减轻小鼠的实验性肾损伤。在本研究中，我们进一步探讨了 miR34a-MV 对单侧输尿管梗阻（UUO）模型肾纤维化的影响。研究方法用过表达 miR-34a 的慢病毒修饰骨髓间充质干细胞，从间充质干细胞上清液中收集 MV。将 C57BL6/J 小鼠分为对照组、单侧输尿管梗阻（UUO）组、UUO + MV 组、UUO + miR-34aMV 组和 UUO + miR-34a 抑制剂-MV 组。手术后向小鼠注射 MV。然后在建模第 7 天和第 14 天对小鼠实施安乐死，并收集肾组织，通过苏木精和伊红、Masson 三色和免疫组织化学（IHC）染色进行进一步分析。结果与 UUO 组相比，UUO + MV 组的肾间质纤维化程度明显减轻，并伴有炎性细胞浸润、肾小管上皮细胞萎缩和空泡变性。令人惊讶的是，过表达 miR-34a 能增强间充质干细胞-间充质干细胞对 UUO 小鼠的上述作用。结论我们的研究表明，miR34a通过调控上皮细胞向间质转化（EMT）和Notch通路，进一步增强了间充质干细胞-MV对小鼠肾脏纤维化的影响，miR-34a可能是治疗肾脏纤维化的候选分子治疗靶点。DOI: 10.52547/ijkd.7673.

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来源期刊

Iranian journal of kidney diseases UROLOGY & NEPHROLOGY-

CiteScore

2.50

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Iranian Journal of Kidney Diseases (IJKD), a peer-reviewed journal in English, is the official publication of the Iranian Society of Nephrology. The aim of the IJKD is the worldwide reflection of the knowledge produced by the scientists and clinicians in nephrology. Published quarterly, the IJKD provides a new platform for advancement of the field. The journal’s objective is to serve as a focal point for debates and exchange of knowledge and experience among researchers in a global context. Original papers, case reports, and invited reviews on all aspects of the kidney diseases, hypertension, dialysis, and transplantation will be covered by the IJKD. Research on the basic science, clinical practice, and socio-economics of renal health are all welcomed by the editors of the journal.