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Notch pathway inhibitor DAPT accelerates in vitro proliferation and adipogenesis in infantile hemangioma stem cells

The Notch signaling pathway is crucial in both adipogenesis and tumor development. It serves a vital role in the development and stability of blood vessels and may be involved in the proliferative phase of infantile hemangiomas, which express various related receptors. Therefore, it was hypothesized...

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Autores principales: Xu, Xing, Wu, Yao, Li, Honghong, Xie, Juan, Cao, Dongsheng, Huang, Xueying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581475/
https://www.ncbi.nlm.nih.gov/pubmed/34777588
http://dx.doi.org/10.3892/ol.2021.13115
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author Xu, Xing
Wu, Yao
Li, Honghong
Xie, Juan
Cao, Dongsheng
Huang, Xueying
author_facet Xu, Xing
Wu, Yao
Li, Honghong
Xie, Juan
Cao, Dongsheng
Huang, Xueying
author_sort Xu, Xing
collection PubMed
description The Notch signaling pathway is crucial in both adipogenesis and tumor development. It serves a vital role in the development and stability of blood vessels and may be involved in the proliferative phase of infantile hemangiomas, which express various related receptors. Therefore, it was hypothesized that the Notch signaling pathway inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, might help accelerate the regression of infantile hemangiomas. The present in vitro study evaluated whether inhibition of the Notch signaling pathway using DAPT could alter adipogenesis in hemangioma stem cells (HemSCs) derived from infantile hemangioma (IH) specimens. A total of 20 infants (age, ≤6 months) with hemangiomas who had not yet received any treatment were selected, and their discarded hemangioma tissues were obtained. HemSCs were isolated from the fresh, sterile IH specimens and treated with DAPT. Reverse transcription-quantitative PCR and western blotting were used to demonstrate the inhibition of the Notch signaling pathway by DAPT. A proliferation assay (Cell Counting Kit-8), oil red O staining, flow cytometry and a transwell assay were used to detect proliferation, adipogenesis, apoptosis and migration of HemSCs. Treatment with DAPT upregulated the expression levels of CCAAT/enhancer-binding protein (C/EBP) α, C/EBPβ, peroxisome proliferator-activated receptor-γ, adiponectin and insulin-like growth factor 1, and promoted the proliferation, apoptosis, migration and lipid accumulation in HemSCs in vitro. Targeting the Notch signaling pathway using DAPT may potentially accelerate the regression of infantile hemangiomas.
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spelling pubmed-85814752021-11-12 Notch pathway inhibitor DAPT accelerates in vitro proliferation and adipogenesis in infantile hemangioma stem cells Xu, Xing Wu, Yao Li, Honghong Xie, Juan Cao, Dongsheng Huang, Xueying Oncol Lett Articles The Notch signaling pathway is crucial in both adipogenesis and tumor development. It serves a vital role in the development and stability of blood vessels and may be involved in the proliferative phase of infantile hemangiomas, which express various related receptors. Therefore, it was hypothesized that the Notch signaling pathway inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, might help accelerate the regression of infantile hemangiomas. The present in vitro study evaluated whether inhibition of the Notch signaling pathway using DAPT could alter adipogenesis in hemangioma stem cells (HemSCs) derived from infantile hemangioma (IH) specimens. A total of 20 infants (age, ≤6 months) with hemangiomas who had not yet received any treatment were selected, and their discarded hemangioma tissues were obtained. HemSCs were isolated from the fresh, sterile IH specimens and treated with DAPT. Reverse transcription-quantitative PCR and western blotting were used to demonstrate the inhibition of the Notch signaling pathway by DAPT. A proliferation assay (Cell Counting Kit-8), oil red O staining, flow cytometry and a transwell assay were used to detect proliferation, adipogenesis, apoptosis and migration of HemSCs. Treatment with DAPT upregulated the expression levels of CCAAT/enhancer-binding protein (C/EBP) α, C/EBPβ, peroxisome proliferator-activated receptor-γ, adiponectin and insulin-like growth factor 1, and promoted the proliferation, apoptosis, migration and lipid accumulation in HemSCs in vitro. Targeting the Notch signaling pathway using DAPT may potentially accelerate the regression of infantile hemangiomas. D.A. Spandidos 2021-12 2021-10-26 /pmc/articles/PMC8581475/ /pubmed/34777588 http://dx.doi.org/10.3892/ol.2021.13115 Text en Copyright: © Xu et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Xu, Xing
Wu, Yao
Li, Honghong
Xie, Juan
Cao, Dongsheng
Huang, Xueying
Notch pathway inhibitor DAPT accelerates in vitro proliferation and adipogenesis in infantile hemangioma stem cells
title Notch pathway inhibitor DAPT accelerates in vitro proliferation and adipogenesis in infantile hemangioma stem cells
title_full Notch pathway inhibitor DAPT accelerates in vitro proliferation and adipogenesis in infantile hemangioma stem cells
title_fullStr Notch pathway inhibitor DAPT accelerates in vitro proliferation and adipogenesis in infantile hemangioma stem cells
title_full_unstemmed Notch pathway inhibitor DAPT accelerates in vitro proliferation and adipogenesis in infantile hemangioma stem cells
title_short Notch pathway inhibitor DAPT accelerates in vitro proliferation and adipogenesis in infantile hemangioma stem cells
title_sort notch pathway inhibitor dapt accelerates in vitro proliferation and adipogenesis in infantile hemangioma stem cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581475/
https://www.ncbi.nlm.nih.gov/pubmed/34777588
http://dx.doi.org/10.3892/ol.2021.13115
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