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The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway
OBJECTIVE: The aim of this study was to investigate the pro-angiogenic potential of olfactory ensheathing cells (OECs) activated by curcumin (CCM) and lipopolysaccharide (LPS) and the possible underlying mechanisms. METHODS: Vascular endothelial cells or tissues were cultured and treated with condit...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895872/ https://www.ncbi.nlm.nih.gov/pubmed/35246244 http://dx.doi.org/10.1186/s13578-022-00765-y |
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author | Wang, Xiaohui Jiang, Chao Zhang, Yongyuan Chen, Zhe Fan, Hong Zhang, Yuyang Wang, Zhiyuan Tian, Fang Li, Jing Yang, Hao Hao, Dingjun |
author_facet | Wang, Xiaohui Jiang, Chao Zhang, Yongyuan Chen, Zhe Fan, Hong Zhang, Yuyang Wang, Zhiyuan Tian, Fang Li, Jing Yang, Hao Hao, Dingjun |
author_sort | Wang, Xiaohui |
collection | PubMed |
description | OBJECTIVE: The aim of this study was to investigate the pro-angiogenic potential of olfactory ensheathing cells (OECs) activated by curcumin (CCM) and lipopolysaccharide (LPS) and the possible underlying mechanisms. METHODS: Vascular endothelial cells or tissues were cultured and treated with conditioned medium (CM) extracted from activated OECs activated through the addition of LPS and CCM or unactivated controls. Concomitantly, the pro-angiogenic potential of OECs was assessed in vitro by aortic ring sprouting assay, endothelial wound healing assay, CCK-8 assay, and tube formation assay. Subsequently, the OECs were co-cultured with endothelial cells to evaluate their promoting effect on endothelial cell proliferation and migration following a mechanical scratch. Moreover, the spinal cord injury (SCI) model in rats was established, and the number of endothelial cells and vascular structure in the injured area after SCI was observed with OEC transplantation. Finally, the underlying mechanism was investigated by western blot analysis of phosphorylated kinase expression with or without the MK-2206 (Akt-inhibitor). RESULT: The present results showed that the activated OECs can effectively promote vascular endothelial cells' proliferation, migration, and vessel-like structure formation. Strikingly, several pro-angiogenic growth factors such as VEGF-A and PDGF-AA, which facilitate vessel formation, were found to be significantly elevated in CM. In addition, the PI3K/Akt signaling pathway was found to be involved in pro-angiogenic events caused by activated OEC CM, displaying higher phosphorylation levels in cells. In contrast, the delivery of MK2206 can effectively abrogate all the positive effects. CONCLUSIONS: OECs activated by LPS and CCM have a pro-angiogenic effect and can effectively promote angiogenesis and improve the microenvironment at the injury site when transplanted in the injured spinal cord. This potentiated ability of OECs to provide pro-angiogenic effects is likely mediated through the PI3K/Akt pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-022-00765-y. |
format | Online Article Text |
id | pubmed-8895872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88958722022-03-10 The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway Wang, Xiaohui Jiang, Chao Zhang, Yongyuan Chen, Zhe Fan, Hong Zhang, Yuyang Wang, Zhiyuan Tian, Fang Li, Jing Yang, Hao Hao, Dingjun Cell Biosci Research OBJECTIVE: The aim of this study was to investigate the pro-angiogenic potential of olfactory ensheathing cells (OECs) activated by curcumin (CCM) and lipopolysaccharide (LPS) and the possible underlying mechanisms. METHODS: Vascular endothelial cells or tissues were cultured and treated with conditioned medium (CM) extracted from activated OECs activated through the addition of LPS and CCM or unactivated controls. Concomitantly, the pro-angiogenic potential of OECs was assessed in vitro by aortic ring sprouting assay, endothelial wound healing assay, CCK-8 assay, and tube formation assay. Subsequently, the OECs were co-cultured with endothelial cells to evaluate their promoting effect on endothelial cell proliferation and migration following a mechanical scratch. Moreover, the spinal cord injury (SCI) model in rats was established, and the number of endothelial cells and vascular structure in the injured area after SCI was observed with OEC transplantation. Finally, the underlying mechanism was investigated by western blot analysis of phosphorylated kinase expression with or without the MK-2206 (Akt-inhibitor). RESULT: The present results showed that the activated OECs can effectively promote vascular endothelial cells' proliferation, migration, and vessel-like structure formation. Strikingly, several pro-angiogenic growth factors such as VEGF-A and PDGF-AA, which facilitate vessel formation, were found to be significantly elevated in CM. In addition, the PI3K/Akt signaling pathway was found to be involved in pro-angiogenic events caused by activated OEC CM, displaying higher phosphorylation levels in cells. In contrast, the delivery of MK2206 can effectively abrogate all the positive effects. CONCLUSIONS: OECs activated by LPS and CCM have a pro-angiogenic effect and can effectively promote angiogenesis and improve the microenvironment at the injury site when transplanted in the injured spinal cord. This potentiated ability of OECs to provide pro-angiogenic effects is likely mediated through the PI3K/Akt pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-022-00765-y. BioMed Central 2022-03-04 /pmc/articles/PMC8895872/ /pubmed/35246244 http://dx.doi.org/10.1186/s13578-022-00765-y 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 Wang, Xiaohui Jiang, Chao Zhang, Yongyuan Chen, Zhe Fan, Hong Zhang, Yuyang Wang, Zhiyuan Tian, Fang Li, Jing Yang, Hao Hao, Dingjun The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway |
title | The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway |
title_full | The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway |
title_fullStr | The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway |
title_full_unstemmed | The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway |
title_short | The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway |
title_sort | promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the pi3k/akt pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8895872/ https://www.ncbi.nlm.nih.gov/pubmed/35246244 http://dx.doi.org/10.1186/s13578-022-00765-y |
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