Arid
DOI10.1093/cvr/cvaa285
Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability
Hollier, Pierre-Louis; Chapouly, Candice; Diop, Aissata; Guimbal, Sarah; Cornuault, Lauriane; Gadeau, Alain-Pierre; Renault, Marie-Ange
通讯作者Renault, MA (corresponding author), Univ Bordeaux, U1034, Biol Cardiovasc Dis, INSERM, 1 Ave Magellan, F-33604 Pessac, France.
来源期刊CARDIOVASCULAR RESEARCH
ISSN0008-6363
EISSN1755-3245
出版年2021
卷号117期号:12页码:2489-2501
英文摘要Aims The therapeutic potential of Hedgehog (Hh) signalling agonists for vascular diseases is of growing interest. However, molecular and cellular mechanisms underlying the role of the Hh signalling in vascular biology remain poorly understood. The purpose of the present article is to clarify some conflicting literature data. Methods and results With this goal, we have demonstrated that, unexpectedly, ectopically administered N-terminal Sonic Hh (N-Shh) and endogenous endothelial-derived Desert Hh (Dhh) induce opposite effects in endothelial cells (ECs). Notably, endothelial Dhh acts under its full-length soluble form (FL-Dhh) and activates Smoothened in ECs, while N-Shh inhibits it. At molecular level, N-Shh prevents FL-Dhh binding to Patched-1 (Ptch1) demonstrating that N-Shh acts as competitive antagonist to FL-Dhh. Besides, we found that even though FL-Hh tigands and N-Hh ligands all bind Ptch1, they induce distinct Ptch1 localization. Finally, we confirmed that in a pathophysiological setting, i.e. brain inflammation, astrocyte-derived N-Shh acts as a FL-Dhh antagonist. Conclusion The present study highlights for the first time that FL-Dhh and N-Hh ligands have antagonistic properties especially in ECs. [GRAPHICS] .
英文关键词Hedgehog signalling Endothelium Permeability Antagonism Multiple sclerosis
类型Article
语种英语
开放获取类型Green Submitted
收录类别SCI-E
WOS记录号WOS:000717498300013
WOS关键词HEDGEHOG SIGNALING PATHWAY ; SONIC HEDGEHOG ; CORONARY VASCULATURE ; ENDOTHELIAL-CELLS ; REPAIR ; RESPONSES ; PROTEIN ; GROWTH ; INJURY
WOS类目Cardiac & Cardiovascular Systems
WOS研究方向Cardiovascular System & Cardiology
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/368053
作者单位[Hollier, Pierre-Louis; Chapouly, Candice; Diop, Aissata; Guimbal, Sarah; Cornuault, Lauriane; Gadeau, Alain-Pierre; Renault, Marie-Ange] Univ Bordeaux, U1034, Biol Cardiovasc Dis, INSERM, 1 Ave Magellan, F-33604 Pessac, France
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Hollier, Pierre-Louis,Chapouly, Candice,Diop, Aissata,et al. Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability[J],2021,117(12):2489-2501.
APA Hollier, Pierre-Louis.,Chapouly, Candice.,Diop, Aissata.,Guimbal, Sarah.,Cornuault, Lauriane.,...&Renault, Marie-Ange.(2021).Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability.CARDIOVASCULAR RESEARCH,117(12),2489-2501.
MLA Hollier, Pierre-Louis,et al."Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability".CARDIOVASCULAR RESEARCH 117.12(2021):2489-2501.
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