Li Zhengmin, He Fang, Dai Shuyang, Yu Qingqing, Si Chenchen, Wu Fan, Zhao Wenxin, Zhang Biyao, Xu Poshi
Department of Medical Laboratory, Fuwai Central China Cardiovascular Hospital, Zhengzhou, Henan, China.
Operating Room, Woman & Infants Hospital of Zhengzhou, Zhengzhou, Henan, China.
Ren Fail. 2025 Dec;47(1):2537797. doi: 10.1080/0886022X.2025.2537797. Epub 2025 Aug 7.
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.
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.
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.
hUCMSCs-Exos protect against AKI by enhancing miR-21-5p/TEAD1 binding and .
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。
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。
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。
hUCMSCs-Exos通过增强miR-21-5p/TEAD1结合发挥对AKI的保护作用。