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源自人脐带间充质干细胞的外泌体通过促进miR-21-5p靶向TEAD1改善心脏手术后的急性肾损伤。

Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate AKI after cardiac surgery by facilitating miR-21-5p targeting TEAD1.

作者信息

Li Zhengmin, He Fang, Dai Shuyang, Yu Qingqing, Si Chenchen, Wu Fan, Zhao Wenxin, Zhang Biyao, Xu Poshi

机构信息

Department of Medical Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, China.

Operating Room, Woman & Infants Hospital of Zhengzhou, Zhengzhou, Henan, China.

出版信息

Ren Fail. 2025 Dec;47(1):2537797. doi: 10.1080/0886022X.2025.2537797. Epub 2025 Aug 7.

DOI:10.1080/0886022X.2025.2537797
PMID:40775738
Abstract

BACKGROUND

Acute kidney injury (AKI) is a common complication of cardiac surgery. Human umbilical cord mesenchymal stem cell (hUCMSC)-derived exosomes affect tissue damage and repair, and miR-21-5p reduces apoptosis and inflammation. However, miR-21-5p's role in cardiac surgery remains unclear.

METHODS

Kidney injury molecule (KIM-1), neutrophil gelatinase-associated lipid carrier protein (NGAL), serum creatinine, and blood urea nitrogen (BUN) levels were tested by enzyme-linked immunosorbent assay. hUCMSCs and exosomes were identified Oil Red O staining kit, alkaline phosphatase staining kit, flow cytometry, transmission electron microscopy, Western blot, and immunofluorescence. Cell viability and apoptosis were detected by cell counting kit 8 and flow cytometry. Interleukin-1β, interleukin-6, and tumor necrosis factor-alpha levels were tested by ELISA kits. Relativity between miR-21-5p and TEA domain family member 1 (TEAD1) was verified by dual-luciferase reporter gene assay and western blot. TEAD1, BUN, and creatinine levels were tested immunohistochemistry and automatic biochemistry analyzer.

RESULTS

KIM-1, NGAL, serum creatinine, and BUN levels were increased and miR-21-5p expression was inhibited in AKI after cardiac surgery. In AKI after cardiac surgery, hUCMSCs-Exos inhibited apoptosis and pyroptosis and promoted viability miR-21-5p regulation. hUCMSCs-Exos retarded AKI after cardiac surgery progression by facilitating miR-21-5p targeting of TEAD1. hUCMSCs-Exos promoted miR-21-5p and inhibited TEAD1 expression . miR-21-5p knockdown facilitated TEAD1 expression . Results were exactly the same and AKI models.

CONCLUSIONS

hUCMSCs-Exos protect against AKI by enhancing miR-21-5p/TEAD1 binding and .

摘要

背景

急性肾损伤(AKI)是心脏手术常见的并发症。人脐带间充质干细胞(hUCMSC)衍生的外泌体影响组织损伤与修复,且miR-21-5p可减少细胞凋亡和炎症。然而,miR-21-5p在心脏手术中的作用仍不明确。

方法

采用酶联免疫吸附测定法检测肾损伤分子(KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、血清肌酐和血尿素氮(BUN)水平。通过油红O染色试剂盒、碱性磷酸酶染色试剂盒、流式细胞术、透射电子显微镜、蛋白质免疫印迹法和免疫荧光法鉴定hUCMSC和外泌体。使用细胞计数试剂盒8和流式细胞术检测细胞活力和凋亡情况。采用ELISA试剂盒检测白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α水平。通过双荧光素酶报告基因测定法和蛋白质免疫印迹法验证miR-21-5p与含TEA结构域家族成员1(TEAD1)之间的相关性。采用免疫组织化学和自动生化分析仪检测TEAD1、BUN和肌酐水平。

结果

心脏手术后AKI患者的KIM-1、NGAL、血清肌酐和BUN水平升高,miR-21-5p表达受到抑制。在心脏手术后的AKI中,hUCMSC衍生的外泌体(hUCMSCs-Exos)通过miR-21-5p调节抑制细胞凋亡和焦亡并促进细胞活力。hUCMSCs-Exos通过促进miR-21-5p靶向TEAD1来延缓心脏手术后AKI的进展。hUCMSCs-Exos促进miR-21-5p表达并抑制TEAD1表达。敲低miR-21-5p可促进TEAD1表达。在AKI模型中结果完全相同。

结论

hUCMSCs-Exos通过增强miR-21-5p/TEAD1结合发挥对AKI的保护作用。

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