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Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investig...

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Autores principales: Lee, Jihyun, Jung, Yujin, Jeong, Seo won, Jeong, Ga Hee, Moon, Gue Tae, Kim, Miri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832320/
https://www.ncbi.nlm.nih.gov/pubmed/33477764
http://dx.doi.org/10.3390/ijms22020931
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author Lee, Jihyun
Jung, Yujin
Jeong, Seo won
Jeong, Ga Hee
Moon, Gue Tae
Kim, Miri
author_facet Lee, Jihyun
Jung, Yujin
Jeong, Seo won
Jeong, Ga Hee
Moon, Gue Tae
Kim, Miri
author_sort Lee, Jihyun
collection PubMed
description The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.
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spelling pubmed-78323202021-01-26 Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model Lee, Jihyun Jung, Yujin Jeong, Seo won Jeong, Ga Hee Moon, Gue Tae Kim, Miri Int J Mol Sci Article The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea. MDPI 2021-01-19 /pmc/articles/PMC7832320/ /pubmed/33477764 http://dx.doi.org/10.3390/ijms22020931 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Jihyun
Jung, Yujin
Jeong, Seo won
Jeong, Ga Hee
Moon, Gue Tae
Kim, Miri
Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model
title Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model
title_full Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model
title_fullStr Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model
title_full_unstemmed Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model
title_short Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model
title_sort inhibition of hippo signaling improves skin lesions in a rosacea-like mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832320/
https://www.ncbi.nlm.nih.gov/pubmed/33477764
http://dx.doi.org/10.3390/ijms22020931
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