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维生素 D3 通过 pAMPKα/Sirt1/Foxo3a 信号通路上调白细胞介素-10 减轻阿霉素诱导的人主动脉内皮细胞衰老。

Vitamin D3 attenuates doxorubicin-induced senescence of human aortic endothelial cells by upregulation of IL-10 via the pAMPKα/Sirt1/Foxo3a signaling pathway.

机构信息

Department of Cardiovascular Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America.

出版信息

PLoS One. 2021 Jun 8;16(6):e0252816. doi: 10.1371/journal.pone.0252816. eCollection 2021.

DOI:10.1371/journal.pone.0252816
PMID:34101754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8186764/
Abstract

The toxicity of doxorubicin to the cardiovascular system often limits its benefits and widespread use as chemotherapy. The mechanisms involved in doxorubicin-induced cardiovascular damage and possible protective interventions are not well-explored. Using human aortic endothelial cells, we show vitamin D3 strongly attenuates doxorubicin-induced senescence and cell cycle arrest. We further show the protective effects of vitamin D3 are mediated by the upregulation of IL-10 and FOXO3a expression through fine modulation of pAMPKα/SIRT1/FOXO3a complex activity. These results have great significance in finding a target for mitigating doxorubicin-induced cardiovascular toxicity.

摘要

阿霉素对心血管系统的毒性常常限制了其作为化疗药物的益处和广泛应用。阿霉素诱导心血管损伤的机制以及可能的保护干预措施尚未得到充分探索。本研究使用人主动脉内皮细胞，发现维生素 D3 可显著减弱阿霉素诱导的衰老和细胞周期停滞。我们进一步表明，维生素 D3 的保护作用是通过精细调节 pAMPKα/SIRT1/FOXO3a 复合物活性，上调白细胞介素-10 和 FOXO3a 的表达来介导的。这些结果对于寻找减轻阿霉素诱导的心血管毒性的靶点具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306e/8186764/721f5e6b7088/pone.0252816.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306e/8186764/16da25115a05/pone.0252816.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306e/8186764/e0870c5a8803/pone.0252816.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306e/8186764/721f5e6b7088/pone.0252816.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306e/8186764/7ce8d187ceaf/pone.0252816.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306e/8186764/79d09b2c0c2c/pone.0252816.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306e/8186764/c4ed74790006/pone.0252816.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306e/8186764/16da25115a05/pone.0252816.g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/306e/8186764/721f5e6b7088/pone.0252816.g006.jpg

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