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High-Mobility Group Box 1 (HMGB1) Induces Migration of Endothelial Progenitor Cell via Receptor for Advanced Glycation End-Products (RAGE)-Dependent PI3K/Akt/eNOS Signaling Pathway

BACKGROUND: High-mobility group box1 (HMGB1) is a cytokine that has been demonstrated to have an important role in inducing migration and homing of endothelial progenitor cells (EPCs) in the process of neovascularization during wound healing, but its specific mechanism remains elusive. The aim of th...

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Autores principales: Zhang, Yulong, You, Bo, Liu, Xinzhu, Chen, Jin, Peng, Yizhi, Yuan, Zhiqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733152/
https://www.ncbi.nlm.nih.gov/pubmed/31461437
http://dx.doi.org/10.12659/MSM.915829
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author Zhang, Yulong
You, Bo
Liu, Xinzhu
Chen, Jin
Peng, Yizhi
Yuan, Zhiqiang
author_facet Zhang, Yulong
You, Bo
Liu, Xinzhu
Chen, Jin
Peng, Yizhi
Yuan, Zhiqiang
author_sort Zhang, Yulong
collection PubMed
description BACKGROUND: High-mobility group box1 (HMGB1) is a cytokine that has been demonstrated to have an important role in inducing migration and homing of endothelial progenitor cells (EPCs) in the process of neovascularization during wound healing, but its specific mechanism remains elusive. The aim of this study was to investigate the effects of the HMGB-RAGE axis in EPC migration, as well as the underlying molecular mechanism responsible for these effects. MATERIAL/METHODS: EPCs were isolated from the mice and identified using flow cytometry and fluorescence staining. The effect of HMGB1 on the activity of EPCs was detected using the Cell Counting Kit-8 (CCK-8). Then, the migration of EPCs was detected by scratch wound-healing and cell migration assay. NO levels were analyzed by ELISA. The expression of p-PI3K, p-Akt, and p-eNOS was determined by Western blot analysis. RAGE expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. F-actin was assessed by fluorescent staining. RESULTS: The results showed that HMGB1 induced a concentration-dependent migration of EPCs, and the migration was RAGE-dependent. The migration could be almost completely blocked by PI3K inhibitors and eNOS inhibitor. HMGB1-RAGE upregulated the expression of p-Akt, p-eNOS, and p-ERK. We also demonstrated that the MEK/ERK signaling pathway is not involved in the EPC migration induced by HMGB1-RAGE. CONCLUSIONS: These data demonstrate that HMGB1 activates RAGE and induces PI3K/Akt/eNOS signaling transduction pathway activation to promote EPC migration. Therefore, the HMGB1-RAGE axis plays an important role in the EPC migration process and may become a potential target in wound healing.
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spelling pubmed-67331522019-09-19 High-Mobility Group Box 1 (HMGB1) Induces Migration of Endothelial Progenitor Cell via Receptor for Advanced Glycation End-Products (RAGE)-Dependent PI3K/Akt/eNOS Signaling Pathway Zhang, Yulong You, Bo Liu, Xinzhu Chen, Jin Peng, Yizhi Yuan, Zhiqiang Med Sci Monit Animal Study BACKGROUND: High-mobility group box1 (HMGB1) is a cytokine that has been demonstrated to have an important role in inducing migration and homing of endothelial progenitor cells (EPCs) in the process of neovascularization during wound healing, but its specific mechanism remains elusive. The aim of this study was to investigate the effects of the HMGB-RAGE axis in EPC migration, as well as the underlying molecular mechanism responsible for these effects. MATERIAL/METHODS: EPCs were isolated from the mice and identified using flow cytometry and fluorescence staining. The effect of HMGB1 on the activity of EPCs was detected using the Cell Counting Kit-8 (CCK-8). Then, the migration of EPCs was detected by scratch wound-healing and cell migration assay. NO levels were analyzed by ELISA. The expression of p-PI3K, p-Akt, and p-eNOS was determined by Western blot analysis. RAGE expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. F-actin was assessed by fluorescent staining. RESULTS: The results showed that HMGB1 induced a concentration-dependent migration of EPCs, and the migration was RAGE-dependent. The migration could be almost completely blocked by PI3K inhibitors and eNOS inhibitor. HMGB1-RAGE upregulated the expression of p-Akt, p-eNOS, and p-ERK. We also demonstrated that the MEK/ERK signaling pathway is not involved in the EPC migration induced by HMGB1-RAGE. CONCLUSIONS: These data demonstrate that HMGB1 activates RAGE and induces PI3K/Akt/eNOS signaling transduction pathway activation to promote EPC migration. Therefore, the HMGB1-RAGE axis plays an important role in the EPC migration process and may become a potential target in wound healing. International Scientific Literature, Inc. 2019-08-28 /pmc/articles/PMC6733152/ /pubmed/31461437 http://dx.doi.org/10.12659/MSM.915829 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Animal Study
Zhang, Yulong
You, Bo
Liu, Xinzhu
Chen, Jin
Peng, Yizhi
Yuan, Zhiqiang
High-Mobility Group Box 1 (HMGB1) Induces Migration of Endothelial Progenitor Cell via Receptor for Advanced Glycation End-Products (RAGE)-Dependent PI3K/Akt/eNOS Signaling Pathway
title High-Mobility Group Box 1 (HMGB1) Induces Migration of Endothelial Progenitor Cell via Receptor for Advanced Glycation End-Products (RAGE)-Dependent PI3K/Akt/eNOS Signaling Pathway
title_full High-Mobility Group Box 1 (HMGB1) Induces Migration of Endothelial Progenitor Cell via Receptor for Advanced Glycation End-Products (RAGE)-Dependent PI3K/Akt/eNOS Signaling Pathway
title_fullStr High-Mobility Group Box 1 (HMGB1) Induces Migration of Endothelial Progenitor Cell via Receptor for Advanced Glycation End-Products (RAGE)-Dependent PI3K/Akt/eNOS Signaling Pathway
title_full_unstemmed High-Mobility Group Box 1 (HMGB1) Induces Migration of Endothelial Progenitor Cell via Receptor for Advanced Glycation End-Products (RAGE)-Dependent PI3K/Akt/eNOS Signaling Pathway
title_short High-Mobility Group Box 1 (HMGB1) Induces Migration of Endothelial Progenitor Cell via Receptor for Advanced Glycation End-Products (RAGE)-Dependent PI3K/Akt/eNOS Signaling Pathway
title_sort high-mobility group box 1 (hmgb1) induces migration of endothelial progenitor cell via receptor for advanced glycation end-products (rage)-dependent pi3k/akt/enos signaling pathway
topic Animal Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733152/
https://www.ncbi.nlm.nih.gov/pubmed/31461437
http://dx.doi.org/10.12659/MSM.915829
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