The proliferation/migration ability mediated by CD151/PI3K/AKT pathway determines the therapeutic effect of hUC-MSCs transplantation on rheumatoid arthritis.

IF 1.5 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE Clinical and Experimental Hypertension Pub Date : 2024-12-31 Epub Date: 2024-06-12 DOI:10.1080/10641963.2024.2366270
Xuewei Xia, Peixin Shen, Guomei Yang, Mengwei Yao, Xiaofeng Wu, Lina Lyu, Yanji He, Zhuxin Li, Wei Wang, Yi Yang, Xiang Ao, Chuanjiang Xia, Zhuo Chen, Xiang Xu
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Abstract

Objective: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment.

Methods: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively.

Results: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs).

Conclusion: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

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CD151/PI3K/AKT 通路介导的增殖/迁移能力决定了 hUC-MSCs 移植对类风湿性关节炎的治疗效果。
目的阐明人脐带间充质干细胞(hUC-MSCs)的增殖和迁移能力决定其治疗类风湿性关节炎疗效的内在机制:方法:利用DBA/1J小鼠建立胶原诱导的RA(CIA)小鼠模型,并验证转染CD151 siRNA的hUC-间充质干细胞的疗效。利用RNA-seq、QT-PCR和Western印迹技术分别评估了PI3K/AKT通路的mRNA和蛋白水平:结果:IFN-γ能明显增强hUC-间充质干细胞的增殖和迁移能力,上调与细胞增殖和迁移相关的基因CD151的表达。通过 CD151 siRNA 处理可有效抑制这种效应。然而,IFN-γ 并不影响 hUC-MSCs 的分化或细胞表面标志物的变化。此外,与空载体处理(siRNA-NC-hUC-MSCs)相比,移植CD151干扰的hUC-MSCs(siRNA-CD151-hUC-MSCs)会导致CIA小鼠足趾定植率下降,治疗效果更差:结论:IFN-γ通过CD151/PI3K/AKT途径促进hUC-间充质干细胞的增殖和迁移。结论:IFN-γ能通过CD151/PI3K/AKT途径促进hUC-间充质干细胞的增殖和迁移,而siRNA-CD151-hUC-间充质干细胞的疗效不如siRNA-NC-hUC-间充质干细胞。
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来源期刊
CiteScore
3.90
自引率
0.80%
发文量
66
审稿时长
6-12 weeks
期刊介绍: Clinical and Experimental Hypertension is a reputable journal that has converted to a full Open Access format starting from Volume 45 in 2023. While previous volumes are still accessible through a Pay to Read model, the journal now provides free and open access to its content. It serves as an international platform for the exchange of up-to-date scientific and clinical information concerning both human and animal hypertension. The journal publishes a wide range of articles, including full research papers, solicited and unsolicited reviews, and commentaries. Through these publications, the journal aims to enhance current understanding and support the timely detection, management, control, and prevention of hypertension-related conditions. One notable aspect of Clinical and Experimental Hypertension is its coverage of special issues that focus on the proceedings of symposia dedicated to hypertension research. This feature allows researchers and clinicians to delve deeper into the latest advancements in this field. The journal is abstracted and indexed in several renowned databases, including Pharmacoeconomics and Outcomes News (Online), Reactions Weekly (Online), CABI, EBSCOhost, Elsevier BV, International Atomic Energy Agency, and the National Library of Medicine, among others. These affiliations ensure that the journal's content receives broad visibility and facilitates its discoverability by professionals and researchers in related disciplines.
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