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STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis

The role of signal transducer and activator of transcription 6 (STAT6) in tumor growth has been widely recognized. However, its effects on the regulation of angiogenesis remain unclear. In this study, we found that STAT6 promoted angiogenesis, possibly by increasing the expression of neuropilin-1 (N...

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Detalles Bibliográficos
Autores principales: Gao, Peng, Ren, Guanghui, Liang, Jiangjiu, Liu, Ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117725/
https://www.ncbi.nlm.nih.gov/pubmed/35600336
http://dx.doi.org/10.3389/fonc.2022.823377
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author Gao, Peng
Ren, Guanghui
Liang, Jiangjiu
Liu, Ju
author_facet Gao, Peng
Ren, Guanghui
Liang, Jiangjiu
Liu, Ju
author_sort Gao, Peng
collection PubMed
description The role of signal transducer and activator of transcription 6 (STAT6) in tumor growth has been widely recognized. However, its effects on the regulation of angiogenesis remain unclear. In this study, we found that STAT6 promoted angiogenesis, possibly by increasing the expression of neuropilin-1 (NRP1) in endothelial cells (ECs). Both STAT6 inhibitor (AS1517499) and STAT6 siRNA reduced EC proliferation, migration, and tube-formation, accompanied by downregulation of NRP1, an angiogenesis regulator. Furthermore, IL-13 induced activation of STAT6 and then increased NRP1 expression in ECs. IL-13-induced EC migration and tube formation were inhibited by NRP1 siRNA. Luciferase assay and chromatin immunoprecipitation assay demonstrated that STAT6 could directly bind to human NRP1 promoter and increase the promoter activity. In tumor xenograft models, inhibition of STAT6 reduced xenograft growth, tumor angiogenesis, and NRP1 expression in vivo. Overall, these results clarified the novel mechanism by which STAT6 regulates angiogenesis, and suggested that STAT6 may be a potential target for anti-angiogenesis therapy.
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spelling pubmed-91177252022-05-20 STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis Gao, Peng Ren, Guanghui Liang, Jiangjiu Liu, Ju Front Oncol Oncology The role of signal transducer and activator of transcription 6 (STAT6) in tumor growth has been widely recognized. However, its effects on the regulation of angiogenesis remain unclear. In this study, we found that STAT6 promoted angiogenesis, possibly by increasing the expression of neuropilin-1 (NRP1) in endothelial cells (ECs). Both STAT6 inhibitor (AS1517499) and STAT6 siRNA reduced EC proliferation, migration, and tube-formation, accompanied by downregulation of NRP1, an angiogenesis regulator. Furthermore, IL-13 induced activation of STAT6 and then increased NRP1 expression in ECs. IL-13-induced EC migration and tube formation were inhibited by NRP1 siRNA. Luciferase assay and chromatin immunoprecipitation assay demonstrated that STAT6 could directly bind to human NRP1 promoter and increase the promoter activity. In tumor xenograft models, inhibition of STAT6 reduced xenograft growth, tumor angiogenesis, and NRP1 expression in vivo. Overall, these results clarified the novel mechanism by which STAT6 regulates angiogenesis, and suggested that STAT6 may be a potential target for anti-angiogenesis therapy. Frontiers Media S.A. 2022-05-05 /pmc/articles/PMC9117725/ /pubmed/35600336 http://dx.doi.org/10.3389/fonc.2022.823377 Text en Copyright © 2022 Gao, Ren, Liang and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Gao, Peng
Ren, Guanghui
Liang, Jiangjiu
Liu, Ju
STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis
title STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis
title_full STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis
title_fullStr STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis
title_full_unstemmed STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis
title_short STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis
title_sort stat6 upregulates nrp1 expression in endothelial cells and promotes angiogenesis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117725/
https://www.ncbi.nlm.nih.gov/pubmed/35600336
http://dx.doi.org/10.3389/fonc.2022.823377
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