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CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis

BACKGROUND: Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, t...

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Autores principales: Sun, Yuanyuan, Jiang, Rong, Hu, Xiaoyi, Gong, Sugang, Wang, Lan, Wu, Wenhui, Li, Jinling, Kang, Xinyang, Xia, Shijin, Liu, Jinming, Zhao, Qinhua, Yuan, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675109/
https://www.ncbi.nlm.nih.gov/pubmed/36403044
http://dx.doi.org/10.1186/s12931-022-02248-7
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author Sun, Yuanyuan
Jiang, Rong
Hu, Xiaoyi
Gong, Sugang
Wang, Lan
Wu, Wenhui
Li, Jinling
Kang, Xinyang
Xia, Shijin
Liu, Jinming
Zhao, Qinhua
Yuan, Ping
author_facet Sun, Yuanyuan
Jiang, Rong
Hu, Xiaoyi
Gong, Sugang
Wang, Lan
Wu, Wenhui
Li, Jinling
Kang, Xinyang
Xia, Shijin
Liu, Jinming
Zhao, Qinhua
Yuan, Ping
author_sort Sun, Yuanyuan
collection PubMed
description BACKGROUND: Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, the mechanism whether circGSAP affects the dysfunction of PEMCs through other microRNAs (miRNAs) remains largely unknown. Therefore, we aimed to demonstrate the underlying mechanisms of circGSAP regulating PMECs dysfunction by absorbing other miRNAs to regulate target genes in idiopathic pulmonary arterial hypertension (IPAH). METHODS: Quantitative real-time polymerase chain reaction, immunofluorescence staining, Cell Counting Kit-8, Calcein-AM/PI staining, Transwell assay, dual-luciferase reporter assay, and ELISA were used to elucidate the roles of circGSAP. RESULTS: Here we showed that plasma circGSAP levels were significantly decreased in patients with IPAH and associated with poor outcomes. In vivo, circGSAP overexpression improved survival, and alleviated pulmonary vascular remodeling of monocrotaline-induced PH (MCT-PH) rats. In vitro, circGSAP overexpression inhibited hypoxia-induced PMECs proliferation, migration and increased mortality by absorbing miR-27a-3p. BMPR2 was identified as a miR-27a-3p target gene. BMPR2 silencing ameliorated the effect of the miR-27a-3p inhibitor on PMECs proliferation,migration and mortality. The levels of BMPR2 were upregulated in circGSAP-overexpressed PMECs and lung tissues of MCT-PH rats. CONCLUSION: Our findings demonstrated that circGSAP alleviated the dysfunction of PMECs via the increase of BMPR2 by competitively binding with miR-27a-3p, and mitigated pulmonary vascular remodeling of MCT-PH rats, providing potential therapeutic strategies for IPAH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02248-7.
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spelling pubmed-96751092022-11-20 CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis Sun, Yuanyuan Jiang, Rong Hu, Xiaoyi Gong, Sugang Wang, Lan Wu, Wenhui Li, Jinling Kang, Xinyang Xia, Shijin Liu, Jinming Zhao, Qinhua Yuan, Ping Respir Res Research BACKGROUND: Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, the mechanism whether circGSAP affects the dysfunction of PEMCs through other microRNAs (miRNAs) remains largely unknown. Therefore, we aimed to demonstrate the underlying mechanisms of circGSAP regulating PMECs dysfunction by absorbing other miRNAs to regulate target genes in idiopathic pulmonary arterial hypertension (IPAH). METHODS: Quantitative real-time polymerase chain reaction, immunofluorescence staining, Cell Counting Kit-8, Calcein-AM/PI staining, Transwell assay, dual-luciferase reporter assay, and ELISA were used to elucidate the roles of circGSAP. RESULTS: Here we showed that plasma circGSAP levels were significantly decreased in patients with IPAH and associated with poor outcomes. In vivo, circGSAP overexpression improved survival, and alleviated pulmonary vascular remodeling of monocrotaline-induced PH (MCT-PH) rats. In vitro, circGSAP overexpression inhibited hypoxia-induced PMECs proliferation, migration and increased mortality by absorbing miR-27a-3p. BMPR2 was identified as a miR-27a-3p target gene. BMPR2 silencing ameliorated the effect of the miR-27a-3p inhibitor on PMECs proliferation,migration and mortality. The levels of BMPR2 were upregulated in circGSAP-overexpressed PMECs and lung tissues of MCT-PH rats. CONCLUSION: Our findings demonstrated that circGSAP alleviated the dysfunction of PMECs via the increase of BMPR2 by competitively binding with miR-27a-3p, and mitigated pulmonary vascular remodeling of MCT-PH rats, providing potential therapeutic strategies for IPAH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02248-7. BioMed Central 2022-11-19 2022 /pmc/articles/PMC9675109/ /pubmed/36403044 http://dx.doi.org/10.1186/s12931-022-02248-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sun, Yuanyuan
Jiang, Rong
Hu, Xiaoyi
Gong, Sugang
Wang, Lan
Wu, Wenhui
Li, Jinling
Kang, Xinyang
Xia, Shijin
Liu, Jinming
Zhao, Qinhua
Yuan, Ping
CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis
title CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis
title_full CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis
title_fullStr CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis
title_full_unstemmed CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis
title_short CircGSAP alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating miR-27a-3p/BMPR2 axis
title_sort circgsap alleviates pulmonary microvascular endothelial cells dysfunction in pulmonary hypertension via regulating mir-27a-3p/bmpr2 axis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9675109/
https://www.ncbi.nlm.nih.gov/pubmed/36403044
http://dx.doi.org/10.1186/s12931-022-02248-7
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