BMSCs 源性外泌体 CISH 通过抑制 NF-κB 通路来刺激巨噬细胞 M2 极化,从而缓解心肌梗死。

IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Cardiovascular Toxicology Pub Date : 2024-04-01 Epub Date: 2024-03-21 DOI:10.1007/s12012-024-09847-4
Minzhi Ouyang, Yang Yang, Guolong Yu, Jiling Zhao, Yi Peng
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引用次数: 0

摘要

目前的心肌梗死(MI)治疗效果不佳,因此有必要深入了解心肌梗死的发病机制。本研究探讨了骨髓间充质干细胞(BMSCs)产生的外泌体(Exo)如何促进心肌梗死的缓解及其治疗潜力。分离的骨髓间充质干细胞通过显微镜、流式细胞仪、茜素红和油红 O 染色法进行鉴定。外显子通过 TEM、NTA 和 Western 印迹进行鉴定。HE 染色、Masson 染色和心功能参数用于评估心肌梗死小鼠的心功能。TUNEL染色、Western印迹和qRT-PCR用于检测细胞凋亡、炎症因子和M1/M2标志物。通过 Western 印迹检测 NF-κB 通路的激活情况。免疫荧光、qRT-PCR、Western印迹和流式细胞术被用来评估巨噬细胞的极化。心肌梗死小鼠表现出心脏损伤、细胞凋亡增加和炎症,而 BMSCs-Exo 治疗可减轻这些影响。在 MI 小鼠中,巨噬细胞 M1 极化增加,NF-κB 通路被激活,而 BMSCs-Exo 治疗可逆转这些变化。此外,MI 小鼠的 CISH 表达减少,但 BMSCs-Exo 治疗后 CISH 表达增加。在体外,LPS 使 RAW264.7 细胞转为 M1 表型并激活 NF-κB 通路,而 BMSCs-Exo 则使其转为 M2 表型并抑制 NF-κB 通路。从机制上讲,BMSCs-Exo通过传递CISH来抑制NF-κB的激活,从而诱导巨噬细胞M2极化。BMSCs-Exo 通过传递 CISH 来抑制 NF-κB 通路,促进巨噬细胞向 M2 型转化,从而缓解 MI。这意味着 BMSCs-Exo 可能是治疗 MI 的有效方法,而 CISH 可能是潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

BMSCs-derived Exosome CISH Alleviates Myocardial Infarction by Inactivating the NF-κB Pathway to Stimulate Macrophage M2 Polarization.

BMSCs-derived Exosome CISH Alleviates Myocardial Infarction by Inactivating the NF-κB Pathway to Stimulate Macrophage M2 Polarization.

Current myocardial infarction (MI) treatments are suboptimal, necessitating deeper pathogenesis understanding of MI. This research explored how exosomes (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) contribute to MI mitigation and their therapeutic potential. Isolated BMSCs was identified by microscope, flow cytometry, alizarin red and oil red O staining. Exo were identified by TEM, NTA and western blot. HE staining, masson staining, and cardiac function parameters were used to assess the cardiac function in MI mice. TUNEL staining, western blot and qRT-PCR were used to detect apoptosis, inflammatory factors and M1/M2 markers. The NF-κB pathway activation was detected through western blot assays. Immunofluorescence, qRT-PCR, western blot, and flow cytometry were employed to evaluate macrophage polarization. MI mice showed cardiac injury, increased apoptosis and inflammation, while BMSCs-Exo treatment alleviated these effects. In MI mice, the macrophage M1 polarization was increased and the NF-κB pathway was activated, whereas BMSCs-Exo treatment reversed these changes. Furthermore, CISH expression was reduced in MI mice, but was elevated with BMSCs-Exo treatment. In vitro, LPS shifted RAW264.7 cells to M1 phenotype and activated the NF-κB pathway, yet BMSCs-Exo shifted them to M2 phenotype and inhibited the NF-κB pathway. Mechanistically, BMSCs-Exo induced macrophage M2 polarization by transmitting CISH to inhibit NF-κB activation. BMSCs-Exo mitigates MI by transmitting CISH to inhibit the NF-κB pathway, promoting macrophages to M2 type. This implies BMSCs-Exo could be a useful treatment for MI, and CISH could be a potential therapy target.

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来源期刊
Cardiovascular Toxicology
Cardiovascular Toxicology 医学-毒理学
CiteScore
6.60
自引率
3.10%
发文量
61
审稿时长
>12 weeks
期刊介绍: Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.
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