A Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB1
Migration of vascular smooth muscle cells (VSMCs) plays an essential role in the development of vascular remodeling in the injured vasculatures. Previous studies have identified high-mobility group box 1 (HMGB1) as a principal effector mediating vascular remodeling; however, the mechanisms involved...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:ac7e3d514f294f3191f7f9ec75b1858c2021-11-04T06:44:46ZA Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB11664-042X10.3389/fphys.2021.775464https://doaj.org/article/ac7e3d514f294f3191f7f9ec75b1858c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.775464/fullhttps://doaj.org/toc/1664-042XMigration of vascular smooth muscle cells (VSMCs) plays an essential role in the development of vascular remodeling in the injured vasculatures. Previous studies have identified high-mobility group box 1 (HMGB1) as a principal effector mediating vascular remodeling; however, the mechanisms involved have not been fully elucidated. Thus, this study investigated the role of HMGB1 on VSMC migration and the underlying molecular mechanisms involved. VSMCs were ex plant cultured using rat thoracic aorta, and the cellular migration was measured using wound-healing assay. Osteopontin (OPN) mRNA and protein were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. The OPN promoter was cloned into pGL3 basic to generate a pLuc-OPN-2284 construct. Migration of VSMCs stimulated with HMGB1 (100ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100–300ng/ml), a neutralizing monoclonal antibody for OPN as well as in cells deficient of OPN. In VSMCs stimulated with HMGB1, OPN mRNA and protein levels were significantly increased in association with an increased promotor activity of OPN gene. Putative-binding sites for activator protein 1 (AP-1) and CCAAT/enhancer-binding protein beta (C/EBPβ) in the indicated promoter region were suggested by TF Search, and the HMGB1-induced expression of OPN was markedly attenuated in cells transfected with siRNA for AP-1. VSMC stimulated with HMGB1 also showed an increased expression of AP-1. Results of this study suggest a pivotal role for AP-1-induced OPN expression in VSMC migration induced by HMGB1. Thus, the AP-1-OPN signaling axis in VSMC might serve as a potential therapeutic target for vascular remodeling in the injured vasculatures.Eun Yeong JeonEun Yeong JeonSeung Eun BaekSeung Eun BaekJi On KimJi On KimJong Min ChoiJong Min ChoiEun Jeong JangChi Dae KimChi Dae KimChi Dae KimFrontiers Media S.A.articlevascular smooth muscle cellshigh-mobility group box 1cell migrationosteopontinactivator protein 1PhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021) |
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vascular smooth muscle cells high-mobility group box 1 cell migration osteopontin activator protein 1 Physiology QP1-981 |
| spellingShingle |
vascular smooth muscle cells high-mobility group box 1 cell migration osteopontin activator protein 1 Physiology QP1-981 Eun Yeong Jeon Eun Yeong Jeon Seung Eun Baek Seung Eun Baek Ji On Kim Ji On Kim Jong Min Choi Jong Min Choi Eun Jeong Jang Chi Dae Kim Chi Dae Kim Chi Dae Kim A Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB1 |
| description |
Migration of vascular smooth muscle cells (VSMCs) plays an essential role in the development of vascular remodeling in the injured vasculatures. Previous studies have identified high-mobility group box 1 (HMGB1) as a principal effector mediating vascular remodeling; however, the mechanisms involved have not been fully elucidated. Thus, this study investigated the role of HMGB1 on VSMC migration and the underlying molecular mechanisms involved. VSMCs were ex plant cultured using rat thoracic aorta, and the cellular migration was measured using wound-healing assay. Osteopontin (OPN) mRNA and protein were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. The OPN promoter was cloned into pGL3 basic to generate a pLuc-OPN-2284 construct. Migration of VSMCs stimulated with HMGB1 (100ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100–300ng/ml), a neutralizing monoclonal antibody for OPN as well as in cells deficient of OPN. In VSMCs stimulated with HMGB1, OPN mRNA and protein levels were significantly increased in association with an increased promotor activity of OPN gene. Putative-binding sites for activator protein 1 (AP-1) and CCAAT/enhancer-binding protein beta (C/EBPβ) in the indicated promoter region were suggested by TF Search, and the HMGB1-induced expression of OPN was markedly attenuated in cells transfected with siRNA for AP-1. VSMC stimulated with HMGB1 also showed an increased expression of AP-1. Results of this study suggest a pivotal role for AP-1-induced OPN expression in VSMC migration induced by HMGB1. Thus, the AP-1-OPN signaling axis in VSMC might serve as a potential therapeutic target for vascular remodeling in the injured vasculatures. |
| format |
article |
| author |
Eun Yeong Jeon Eun Yeong Jeon Seung Eun Baek Seung Eun Baek Ji On Kim Ji On Kim Jong Min Choi Jong Min Choi Eun Jeong Jang Chi Dae Kim Chi Dae Kim Chi Dae Kim |
| author_facet |
Eun Yeong Jeon Eun Yeong Jeon Seung Eun Baek Seung Eun Baek Ji On Kim Ji On Kim Jong Min Choi Jong Min Choi Eun Jeong Jang Chi Dae Kim Chi Dae Kim Chi Dae Kim |
| author_sort |
Eun Yeong Jeon |
| title |
A Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB1 |
| title_short |
A Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB1 |
| title_full |
A Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB1 |
| title_fullStr |
A Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB1 |
| title_full_unstemmed |
A Pivotal Role for AP-1-Mediated Osteopontin Expression in the Increased Migration of Vascular Smooth Muscle Cells Stimulated With HMGB1 |
| title_sort |
pivotal role for ap-1-mediated osteopontin expression in the increased migration of vascular smooth muscle cells stimulated with hmgb1 |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/ac7e3d514f294f3191f7f9ec75b1858c |
| work_keys_str_mv |
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