IL-28A/IL-10Rβ 轴通过调节 HSP70-1 的表达,通过 eNOS/AKT 信号和 AP-1/NF-κB/MMP-2 网络促进血管生成。

Jun-Hui Song, Byungdoo Hwang, Sung Lyea Park, Hoon Kim, Soontag Jung, Changsun Choi, Hwan Myung Lee, Seok-Joong Yun, Yung Hyun Choi, Eun-Jong Cha, Cam Patterson, Wun-Jae Kim, Sung-Kwon Moon
{"title":"IL-28A/IL-10Rβ 轴通过调节 HSP70-1 的表达,通过 eNOS/AKT 信号和 AP-1/NF-κB/MMP-2 网络促进血管生成。","authors":"Jun-Hui Song, Byungdoo Hwang, Sung Lyea Park, Hoon Kim, Soontag Jung, Changsun Choi, Hwan Myung Lee, Seok-Joong Yun, Yung Hyun Choi, Eun-Jong Cha, Cam Patterson, Wun-Jae Kim, Sung-Kwon Moon","doi":"10.1016/j.jare.2024.08.013","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Angiogenesis plays a significant role in the development of tumor progression and inflammatory diseases. The role of IL-28A in angiogenesis and its precise regulatory mechanisms remain rarely elucidated.</p><p><strong>Objectives: </strong>We report the novel regulatory role of IL-28A in physiological angiogenesis. The study aimed to elucidate the regulatory mechanisms involved in IL-28A-mediated angiogenesis and identify key genes associated with IL-28A-induced angiogenic responses.</p><p><strong>Methods: </strong>To know the effect of IL-28A on angiogenesis, HUVECs were applied to perform proliferation, migration, invasion, tube formation, immunoblot, and EMSA. Gene expression changes in HUVECs following IL-28A treatment were analyzed by NGS. The functional role of HSP70-1 and IL-10Rβ in IL-28A-induced angiogenic responses was evaluated using PCR and siRNA knockdown. Animal studies were conducted by aortic ring ex vivo assays, Matrigel plug in vivo assays, and immunochemistry using HSP70-1 knockout and transgenic mice models. The efficacy of IL-28A in angiogenesis was confirmed in a hind-limb ischemia model.</p><p><strong>Results: </strong>Autocrine/paracrine actions in HUVECs regulated IL-28A protein expression. Exogenous IL-28A increased the proliferation of HUVECs via eNOS/AKT and ERK1/2 signaling. IL-28A treatment promoted migration, invasion, and capillary tube formation of HUVECs through induction of the AP-1/NF-κB/MMP-2 network, which was associated with eNOS/AKT and ERK1/2 signaling. The efficacy of IL-28A-induced angiogenic potential was confirmed by aortic ring and Matrigel plug assay. HSP70-1 was identified as an IL-28A-mediated angiogenic effector gene using bioinformatics. Knockdown of HSP70-1 abolished angiogenic responses and eNOS/AKT signaling in IL-28A-treated HUVECs. IL-28A-induced microvessel sprouting formation was testified in HSP70-1-deficient and HSP70-1 transgenic mice. Flow recovery in hind-limb ischemia mice was accelerated by IL-28A injection. Finally, ablation of the IL-10Rβ gene impeded the angiogenic responses and eNOS/AKT signaling stimulated by IL-28A in HUVECs.</p><p><strong>Conclusion: </strong>HSP70-1 drives the progression of angiogenesis by the IL-28A/IL-10Rβ axis via eNOS/AKT signaling and the AP-1/NF-κB/MMP-2 network.</p>","PeriodicalId":94063,"journal":{"name":"Journal of advanced research","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression.\",\"authors\":\"Jun-Hui Song, Byungdoo Hwang, Sung Lyea Park, Hoon Kim, Soontag Jung, Changsun Choi, Hwan Myung Lee, Seok-Joong Yun, Yung Hyun Choi, Eun-Jong Cha, Cam Patterson, Wun-Jae Kim, Sung-Kwon Moon\",\"doi\":\"10.1016/j.jare.2024.08.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Angiogenesis plays a significant role in the development of tumor progression and inflammatory diseases. The role of IL-28A in angiogenesis and its precise regulatory mechanisms remain rarely elucidated.</p><p><strong>Objectives: </strong>We report the novel regulatory role of IL-28A in physiological angiogenesis. The study aimed to elucidate the regulatory mechanisms involved in IL-28A-mediated angiogenesis and identify key genes associated with IL-28A-induced angiogenic responses.</p><p><strong>Methods: </strong>To know the effect of IL-28A on angiogenesis, HUVECs were applied to perform proliferation, migration, invasion, tube formation, immunoblot, and EMSA. Gene expression changes in HUVECs following IL-28A treatment were analyzed by NGS. The functional role of HSP70-1 and IL-10Rβ in IL-28A-induced angiogenic responses was evaluated using PCR and siRNA knockdown. Animal studies were conducted by aortic ring ex vivo assays, Matrigel plug in vivo assays, and immunochemistry using HSP70-1 knockout and transgenic mice models. The efficacy of IL-28A in angiogenesis was confirmed in a hind-limb ischemia model.</p><p><strong>Results: </strong>Autocrine/paracrine actions in HUVECs regulated IL-28A protein expression. Exogenous IL-28A increased the proliferation of HUVECs via eNOS/AKT and ERK1/2 signaling. IL-28A treatment promoted migration, invasion, and capillary tube formation of HUVECs through induction of the AP-1/NF-κB/MMP-2 network, which was associated with eNOS/AKT and ERK1/2 signaling. The efficacy of IL-28A-induced angiogenic potential was confirmed by aortic ring and Matrigel plug assay. HSP70-1 was identified as an IL-28A-mediated angiogenic effector gene using bioinformatics. Knockdown of HSP70-1 abolished angiogenic responses and eNOS/AKT signaling in IL-28A-treated HUVECs. IL-28A-induced microvessel sprouting formation was testified in HSP70-1-deficient and HSP70-1 transgenic mice. Flow recovery in hind-limb ischemia mice was accelerated by IL-28A injection. Finally, ablation of the IL-10Rβ gene impeded the angiogenic responses and eNOS/AKT signaling stimulated by IL-28A in HUVECs.</p><p><strong>Conclusion: </strong>HSP70-1 drives the progression of angiogenesis by the IL-28A/IL-10Rβ axis via eNOS/AKT signaling and the AP-1/NF-κB/MMP-2 network.</p>\",\"PeriodicalId\":94063,\"journal\":{\"name\":\"Journal of advanced research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of advanced research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jare.2024.08.013\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of advanced research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.jare.2024.08.013","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

导言:血管生成在肿瘤进展和炎症性疾病的发展中起着重要作用。IL-28A在血管生成中的作用及其精确调控机制仍很少被阐明:我们报告了IL-28A在生理性血管生成中的新型调控作用。研究旨在阐明IL-28A介导的血管生成的调控机制,并确定与IL-28A诱导的血管生成反应相关的关键基因:为了了解IL-28A对血管生成的影响,应用HUVECs进行增殖、迁移、侵袭、管形成、免疫印迹和EMSA。通过 NGS 分析了 IL-28A 处理后 HUVECs 的基因表达变化。利用 PCR 和 siRNA 敲除技术评估了 HSP70-1 和 IL-10Rβ 在 IL-28A 诱导的血管生成反应中的功能作用。通过主动脉环体外试验、Matrigel塞体内试验以及使用HSP70-1基因敲除和转基因小鼠模型的免疫化学方法进行了动物实验。在后肢缺血模型中证实了IL-28A对血管生成的功效:结果:HUVECs的自分泌/旁分泌作用调节了IL-28A蛋白的表达。外源性 IL-28A 通过 eNOS/AKT 和 ERK1/2 信号传导增加了 HUVECs 的增殖。IL-28A通过诱导AP-1/NF-κB/MMP-2网络促进了HUVECs的迁移、侵袭和毛细血管管的形成,这与eNOS/AKT和ERK1/2信号有关。主动脉环和 Matrigel 栓实验证实了 IL-28A 诱导血管生成潜能的功效。利用生物信息学方法确定了HSP70-1是IL-28A介导的血管生成效应基因。敲除HSP70-1可消除IL-28A处理的HUVECs的血管生成反应和eNOS/AKT信号传导。在HSP70-1缺陷小鼠和HSP70-1转基因小鼠中,IL-28A诱导的微血管发芽形成得到了验证。注射 IL-28A 加快了后肢缺血小鼠的血流恢复。最后,IL-10Rβ基因的消减阻碍了IL-28A刺激HUVECs的血管生成反应和eNOS/AKT信号转导:结论:HSP70-1通过eNOS/AKT信号和AP-1/NF-κB/MMP-2网络驱动IL-28A/IL-10Rβ轴促进血管生成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression.

Introduction: Angiogenesis plays a significant role in the development of tumor progression and inflammatory diseases. The role of IL-28A in angiogenesis and its precise regulatory mechanisms remain rarely elucidated.

Objectives: We report the novel regulatory role of IL-28A in physiological angiogenesis. The study aimed to elucidate the regulatory mechanisms involved in IL-28A-mediated angiogenesis and identify key genes associated with IL-28A-induced angiogenic responses.

Methods: To know the effect of IL-28A on angiogenesis, HUVECs were applied to perform proliferation, migration, invasion, tube formation, immunoblot, and EMSA. Gene expression changes in HUVECs following IL-28A treatment were analyzed by NGS. The functional role of HSP70-1 and IL-10Rβ in IL-28A-induced angiogenic responses was evaluated using PCR and siRNA knockdown. Animal studies were conducted by aortic ring ex vivo assays, Matrigel plug in vivo assays, and immunochemistry using HSP70-1 knockout and transgenic mice models. The efficacy of IL-28A in angiogenesis was confirmed in a hind-limb ischemia model.

Results: Autocrine/paracrine actions in HUVECs regulated IL-28A protein expression. Exogenous IL-28A increased the proliferation of HUVECs via eNOS/AKT and ERK1/2 signaling. IL-28A treatment promoted migration, invasion, and capillary tube formation of HUVECs through induction of the AP-1/NF-κB/MMP-2 network, which was associated with eNOS/AKT and ERK1/2 signaling. The efficacy of IL-28A-induced angiogenic potential was confirmed by aortic ring and Matrigel plug assay. HSP70-1 was identified as an IL-28A-mediated angiogenic effector gene using bioinformatics. Knockdown of HSP70-1 abolished angiogenic responses and eNOS/AKT signaling in IL-28A-treated HUVECs. IL-28A-induced microvessel sprouting formation was testified in HSP70-1-deficient and HSP70-1 transgenic mice. Flow recovery in hind-limb ischemia mice was accelerated by IL-28A injection. Finally, ablation of the IL-10Rβ gene impeded the angiogenic responses and eNOS/AKT signaling stimulated by IL-28A in HUVECs.

Conclusion: HSP70-1 drives the progression of angiogenesis by the IL-28A/IL-10Rβ axis via eNOS/AKT signaling and the AP-1/NF-κB/MMP-2 network.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
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:481959085
Book学术官方微信