Vascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo

Yuhan Chen,1,* Yuanyuan Chen,1,* Xueze Jiang,1 Mengkun Shi,2 Zhenwei Yang,1 Zhiyong Chen,1 Xuesheng Hua,1 Jie Chen,1 Yuepeng Wang1 1Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Cardi...

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Autores principales:	Chen Y, Jiang X, Shi M, Yang Z, Chen Z, Hua X, Chen J, Wang Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	vascular adventitial fibroblasts vascular smooth muscle cells fgf10 proliferation migration neointima formation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/3ab1341fc7464b64ae9eae11e9056582
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spelling	oai:doaj.org-article:3ab1341fc7464b64ae9eae11e90565822021-12-02T15:43:56ZVascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo1178-7031https://doaj.org/article/3ab1341fc7464b64ae9eae11e90565822021-05-01T00:00:00Zhttps://www.dovepress.com/vascular-adventitial-fibroblasts-derived-fgf10-promotes-vascular-smoot-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Yuhan Chen,1,* Yuanyuan Chen,1,* Xueze Jiang,1 Mengkun Shi,2 Zhenwei Yang,1 Zhiyong Chen,1 Xuesheng Hua,1 Jie Chen,1 Yuepeng Wang1 1Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuepeng Wang; Jie ChenDepartment of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People’s Republic of ChinaTel +86 18217267289; +86 15280380968Email wangyuepeng@xinhuamed.com.cn; jieyuepeng@msn.comBackground: Activation of vascular adventitial fibroblasts (VAFs) upon vascular injury contributes greatly to the medial vascular smooth muscle cells (VSMCs) proliferation, migration and the subsequent neointima formation. A number of factors including fibroblast growth factors (FGFs) have been shown to control VSMC growth, proliferation and phenotypic switching, suggesting that they may function as paracrine signals for VAFs to modulate VSMCs functions. However, little is known about the signaling molecule(s) and its mechanism of action. This study is set to identify which and how FGF family members are involved in VAFs mediated vascular remodeling.Methods: We used qPCR, Western blot and Immunohistochemistry to observe the spatiotemporal expression of FGF10 and FGFR2 in injured vascular tissue. The proliferation and migration assays of VSMCs were performed in a co-culture system. The activation of signaling pathway was detected by Western blot, immunohistochemistry and immunofluorescence. Hematoxylin-eosin and immunofluorescence were used to assess the effects of exogenous FGF10 and siFGF10 on the neointima formation.Results: The expression of FGF10 and FGFR2 were increased from day 3 through day 14 post injury. FGF10 was significantly upregulated in adventitia, and FGFR2 was detected in both media and neointima after injury. In vitro, FGF10 was most prominently expressed in VAFs and FGFR2 was significantly expressed in VSMCs. Both were regulated by PDGF. Co-culture of VAFs and VSMCs in vitro showed that VAF-derived FGF10 promoted the proliferation and migration of VSMCs. PDGF could synergistically enhance the process. VAF-derived FGF10 can significantly activate the FGFR2 in VSMCs and furthermore significantly activate the downstream MAPK/PI3K-AKT signaling pathways. Delivery of exogenous FGF10 potentiated the neointima formation, while siFGF10 attenuated the neointima formation.Conclusion: VAFs-derived FGF10 promoted the proliferation and migration of VSMCs and neointima formation, and FGF10-FGFR2 signaling triggered the activation of MAPK/PI3K-AKT pathways in VSMCs and PDGF synergistically amplified FGF10 signaling.Keywords: vascular adventitial fibroblasts, vascular smooth muscle cells, FGF10, proliferation, migration, neointima formationChen YChen YJiang XShi MYang ZChen ZHua XChen JWang YDove Medical Pressarticlevascular adventitial fibroblastsvascular smooth muscle cellsfgf10proliferationmigrationneointima formationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 2207-2223 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	vascular adventitial fibroblasts vascular smooth muscle cells fgf10 proliferation migration neointima formation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	vascular adventitial fibroblasts vascular smooth muscle cells fgf10 proliferation migration neointima formation Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Chen Y Chen Y Jiang X Shi M Yang Z Chen Z Hua X Chen J Wang Y Vascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo
description	Yuhan Chen,1,* Yuanyuan Chen,1,* Xueze Jiang,1 Mengkun Shi,2 Zhenwei Yang,1 Zhiyong Chen,1 Xuesheng Hua,1 Jie Chen,1 Yuepeng Wang1 1Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuepeng Wang; Jie ChenDepartment of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, People’s Republic of ChinaTel +86 18217267289; +86 15280380968Email wangyuepeng@xinhuamed.com.cn; jieyuepeng@msn.comBackground: Activation of vascular adventitial fibroblasts (VAFs) upon vascular injury contributes greatly to the medial vascular smooth muscle cells (VSMCs) proliferation, migration and the subsequent neointima formation. A number of factors including fibroblast growth factors (FGFs) have been shown to control VSMC growth, proliferation and phenotypic switching, suggesting that they may function as paracrine signals for VAFs to modulate VSMCs functions. However, little is known about the signaling molecule(s) and its mechanism of action. This study is set to identify which and how FGF family members are involved in VAFs mediated vascular remodeling.Methods: We used qPCR, Western blot and Immunohistochemistry to observe the spatiotemporal expression of FGF10 and FGFR2 in injured vascular tissue. The proliferation and migration assays of VSMCs were performed in a co-culture system. The activation of signaling pathway was detected by Western blot, immunohistochemistry and immunofluorescence. Hematoxylin-eosin and immunofluorescence were used to assess the effects of exogenous FGF10 and siFGF10 on the neointima formation.Results: The expression of FGF10 and FGFR2 were increased from day 3 through day 14 post injury. FGF10 was significantly upregulated in adventitia, and FGFR2 was detected in both media and neointima after injury. In vitro, FGF10 was most prominently expressed in VAFs and FGFR2 was significantly expressed in VSMCs. Both were regulated by PDGF. Co-culture of VAFs and VSMCs in vitro showed that VAF-derived FGF10 promoted the proliferation and migration of VSMCs. PDGF could synergistically enhance the process. VAF-derived FGF10 can significantly activate the FGFR2 in VSMCs and furthermore significantly activate the downstream MAPK/PI3K-AKT signaling pathways. Delivery of exogenous FGF10 potentiated the neointima formation, while siFGF10 attenuated the neointima formation.Conclusion: VAFs-derived FGF10 promoted the proliferation and migration of VSMCs and neointima formation, and FGF10-FGFR2 signaling triggered the activation of MAPK/PI3K-AKT pathways in VSMCs and PDGF synergistically amplified FGF10 signaling.Keywords: vascular adventitial fibroblasts, vascular smooth muscle cells, FGF10, proliferation, migration, neointima formation
format	article
author	Chen Y Chen Y Jiang X Shi M Yang Z Chen Z Hua X Chen J Wang Y
author_facet	Chen Y Chen Y Jiang X Shi M Yang Z Chen Z Hua X Chen J Wang Y
author_sort	Chen Y
title	Vascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo
title_short	Vascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo
title_full	Vascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo
title_fullStr	Vascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo
title_full_unstemmed	Vascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo
title_sort	vascular adventitial fibroblasts-derived fgf10 promotes vascular smooth muscle cells proliferation and migration in vitro and the neointima formation in vivo
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/3ab1341fc7464b64ae9eae11e9056582
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Vascular Adventitial Fibroblasts-Derived FGF10 Promotes Vascular Smooth Muscle Cells Proliferation and Migration in vitro and the Neointima Formation in vivo

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