Adipose Mesenchymal Stem Cell-Derived Exosomes in Conjunction with Roflumilast Ameliorate Chronic Kidney Disease Through the Modulation of Fibrosis and Inflammation.

IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS
Mohamed Ali, Mohamed H Sherif, Nashwa Barakat, Bassant Yahia, Ahmed A Shokeir, Basel Sitohy
{"title":"Adipose Mesenchymal Stem Cell-Derived Exosomes in Conjunction with Roflumilast Ameliorate Chronic Kidney Disease Through the Modulation of Fibrosis and Inflammation.","authors":"Mohamed Ali, Mohamed H Sherif, Nashwa Barakat, Bassant Yahia, Ahmed A Shokeir, Basel Sitohy","doi":"10.1002/adbi.202500152","DOIUrl":null,"url":null,"abstract":"<p><p>Adipose mesenchymal stem cell-derived exosomes and the PDE4 inhibitor roflumilast (ROF) are investigated as potential treatments for chronic kidney disease (CKD). The exosomes are extracted and analyzed using electron microscopy and flow cytometry, then employed with ROF for in vivo implantation in a CKD animal model. Animals aredivided into seven groups. Group (I) Control; (II) exosomes; (III) ROF; (IV) Adriamycin (ADR); (V) ADR + exosomes, (VI) ADR + ROF, and (VII) ADR + Exosomes+ ROF. Biochemical serum indicators (creatinine, BUN), antioxidant status (GSH, MDA), and the mRNA expressions of TGF-β1, Smad3, IL-6, BAX, Wnt-7, FN, and miRNA145-5p are determined using qRT-PCR. Histology assessment using H&E staining, ultrastructural observation using TEM, and protein expression in kidney tissue (FN1 and BAX) are assessed. The isolated exosomes showed cup-shaped morphologyand expressed CD81, CD9, and CD63. Exosomes and ROF increased glutathione (GSH) levels while decreasing malondialdehyde (MDA) levels. Further, ROF and exosomes treatment lowered the expression of the apoptotic indicators BAX, the fibrotic markers TGFβ1, Smad3, Wnt7a, and FN1, and the inflammatory marker IL6, and increased the expression of miRNA-145. Moreover, ROF and exosomes improved histological and ultrastructural examination. In conclusion, exosomes and ROF can protect against CKD by reducing apoptosis and fibrosis.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00152"},"PeriodicalIF":2.6000,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/adbi.202500152","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0

Abstract

Adipose mesenchymal stem cell-derived exosomes and the PDE4 inhibitor roflumilast (ROF) are investigated as potential treatments for chronic kidney disease (CKD). The exosomes are extracted and analyzed using electron microscopy and flow cytometry, then employed with ROF for in vivo implantation in a CKD animal model. Animals aredivided into seven groups. Group (I) Control; (II) exosomes; (III) ROF; (IV) Adriamycin (ADR); (V) ADR + exosomes, (VI) ADR + ROF, and (VII) ADR + Exosomes+ ROF. Biochemical serum indicators (creatinine, BUN), antioxidant status (GSH, MDA), and the mRNA expressions of TGF-β1, Smad3, IL-6, BAX, Wnt-7, FN, and miRNA145-5p are determined using qRT-PCR. Histology assessment using H&E staining, ultrastructural observation using TEM, and protein expression in kidney tissue (FN1 and BAX) are assessed. The isolated exosomes showed cup-shaped morphologyand expressed CD81, CD9, and CD63. Exosomes and ROF increased glutathione (GSH) levels while decreasing malondialdehyde (MDA) levels. Further, ROF and exosomes treatment lowered the expression of the apoptotic indicators BAX, the fibrotic markers TGFβ1, Smad3, Wnt7a, and FN1, and the inflammatory marker IL6, and increased the expression of miRNA-145. Moreover, ROF and exosomes improved histological and ultrastructural examination. In conclusion, exosomes and ROF can protect against CKD by reducing apoptosis and fibrosis.

脂肪间充质干细胞衍生外泌体联合罗氟米司特通过调节纤维化和炎症改善慢性肾脏疾病。
脂肪间充质干细胞衍生的外泌体和PDE4抑制剂罗氟米司特(ROF)被研究作为慢性肾脏疾病(CKD)的潜在治疗方法。通过电镜和流式细胞术提取外泌体并进行分析,然后与ROF一起在体内植入CKD动物模型。动物被分为七类。(一)控制组;(2)液;(3)学院;(四)阿霉素(ADR);(V) ADR +外泌体、(VI) ADR + ROF、(VII) ADR +外泌体+ ROF,采用qRT-PCR检测血清生化指标(肌酐、BUN)、抗氧化状态(GSH、MDA)以及TGF-β1、Smad3、IL-6、BAX、Wnt-7、FN、miRNA145-5p mRNA表达。采用H&E染色进行组织学评价,透射电镜观察超微结构,观察肾组织蛋白表达(FN1和BAX)。分离的外泌体呈杯状,表达CD81、CD9和CD63。外泌体和ROF增加谷胱甘肽(GSH)水平,同时降低丙二醛(MDA)水平。此外,ROF和外泌体处理降低了凋亡指标BAX、纤维化标志物tgf - β1、Smad3、Wnt7a和FN1以及炎症标志物IL6的表达,增加了miRNA-145的表达。此外,ROF和外泌体改善了组织学和超微结构检查。综上所述,外泌体和ROF可以通过减少细胞凋亡和纤维化来预防CKD。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Advanced biology
Advanced biology Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
6.60
自引率
0.00%
发文量
130
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信