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Effects of Different Ligands in the Notch Signaling Pathway on the Proliferation and Transdifferentiation of Primary Type II Alveolar Epithelial Cells

Background: Transdifferentiation of type II alveolar epithelial cells (AECII) into type I alveolar epithelial cells (AECI) is involved in neonatal respiratory distress syndrome (NRDS). Different ligands of the Notch pathway could have different effects on AECII transdifferentiation. Objective: To in...

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Autores principales: Liu, Xiuxiang, Zhu, Xiaoxi, Zhu, Guoqing, Wang, Chaoyun, Gao, Ruiwei, Ma, Jinshuai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424003/
https://www.ncbi.nlm.nih.gov/pubmed/32850559
http://dx.doi.org/10.3389/fped.2020.00452
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author Liu, Xiuxiang
Zhu, Xiaoxi
Zhu, Guoqing
Wang, Chaoyun
Gao, Ruiwei
Ma, Jinshuai
author_facet Liu, Xiuxiang
Zhu, Xiaoxi
Zhu, Guoqing
Wang, Chaoyun
Gao, Ruiwei
Ma, Jinshuai
author_sort Liu, Xiuxiang
collection PubMed
description Background: Transdifferentiation of type II alveolar epithelial cells (AECII) into type I alveolar epithelial cells (AECI) is involved in neonatal respiratory distress syndrome (NRDS). Different ligands of the Notch pathway could have different effects on AECII transdifferentiation. Objective: To investigate the effects of Dlk1 and Jagged1 on the proliferation and transdifferentiation of AECII. Methods: Fetal AECIIs (19 days of gestation) were divided: control group, Dlk1 group, rhNF-κB group. Proliferation was tested using the MTT assay. Expression of surfactant protein C (SP-C) and aquaporin 5 (AQP5) was examined by immunofluorescence. mRNA and protein levels of SP-C, AQP5, Nortch1, Dlk1, Jagged1, and Hes1 were examined by RT-PCR and western blot. Results: In response to Dlk1, cell number and proliferation were increased (P < 0.05), and mRNA and protein levels of SP-C, Dlk1, Notch1, and Hes1 were up-regulated, while AQP and Jagged1 were decreased. In response to rhNF-κB, the cell number and proliferation were reduced, and mRNA and protein levels of Jagged1 and Notch1 were up-regulated, while Dlk1, and SP-C were downregulated. In the Dlk1 group, SP-C, and AQP5 expression patterns suggested that the cells were still transdifferentiating by 96 h, while in the rhNF-κB group, most cells had transdifferentiated by 72 h and were close to apoptosis by 96 h. Conclusion: These results suggest that Dlk1 promoted proliferation of AECIIs and inhibited cell transdifferentiation, while Jagged1 treatment inhibited proliferation of AECIIs and promoted transdifferentiation to AECIs. These results provide some clue for the eventual management of NDRS.
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spelling pubmed-74240032020-08-25 Effects of Different Ligands in the Notch Signaling Pathway on the Proliferation and Transdifferentiation of Primary Type II Alveolar Epithelial Cells Liu, Xiuxiang Zhu, Xiaoxi Zhu, Guoqing Wang, Chaoyun Gao, Ruiwei Ma, Jinshuai Front Pediatr Pediatrics Background: Transdifferentiation of type II alveolar epithelial cells (AECII) into type I alveolar epithelial cells (AECI) is involved in neonatal respiratory distress syndrome (NRDS). Different ligands of the Notch pathway could have different effects on AECII transdifferentiation. Objective: To investigate the effects of Dlk1 and Jagged1 on the proliferation and transdifferentiation of AECII. Methods: Fetal AECIIs (19 days of gestation) were divided: control group, Dlk1 group, rhNF-κB group. Proliferation was tested using the MTT assay. Expression of surfactant protein C (SP-C) and aquaporin 5 (AQP5) was examined by immunofluorescence. mRNA and protein levels of SP-C, AQP5, Nortch1, Dlk1, Jagged1, and Hes1 were examined by RT-PCR and western blot. Results: In response to Dlk1, cell number and proliferation were increased (P < 0.05), and mRNA and protein levels of SP-C, Dlk1, Notch1, and Hes1 were up-regulated, while AQP and Jagged1 were decreased. In response to rhNF-κB, the cell number and proliferation were reduced, and mRNA and protein levels of Jagged1 and Notch1 were up-regulated, while Dlk1, and SP-C were downregulated. In the Dlk1 group, SP-C, and AQP5 expression patterns suggested that the cells were still transdifferentiating by 96 h, while in the rhNF-κB group, most cells had transdifferentiated by 72 h and were close to apoptosis by 96 h. Conclusion: These results suggest that Dlk1 promoted proliferation of AECIIs and inhibited cell transdifferentiation, while Jagged1 treatment inhibited proliferation of AECIIs and promoted transdifferentiation to AECIs. These results provide some clue for the eventual management of NDRS. Frontiers Media S.A. 2020-08-06 /pmc/articles/PMC7424003/ /pubmed/32850559 http://dx.doi.org/10.3389/fped.2020.00452 Text en Copyright © 2020 Liu, Zhu, Zhu, Wang, Gao and Ma. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Liu, Xiuxiang
Zhu, Xiaoxi
Zhu, Guoqing
Wang, Chaoyun
Gao, Ruiwei
Ma, Jinshuai
Effects of Different Ligands in the Notch Signaling Pathway on the Proliferation and Transdifferentiation of Primary Type II Alveolar Epithelial Cells
title Effects of Different Ligands in the Notch Signaling Pathway on the Proliferation and Transdifferentiation of Primary Type II Alveolar Epithelial Cells
title_full Effects of Different Ligands in the Notch Signaling Pathway on the Proliferation and Transdifferentiation of Primary Type II Alveolar Epithelial Cells
title_fullStr Effects of Different Ligands in the Notch Signaling Pathway on the Proliferation and Transdifferentiation of Primary Type II Alveolar Epithelial Cells
title_full_unstemmed Effects of Different Ligands in the Notch Signaling Pathway on the Proliferation and Transdifferentiation of Primary Type II Alveolar Epithelial Cells
title_short Effects of Different Ligands in the Notch Signaling Pathway on the Proliferation and Transdifferentiation of Primary Type II Alveolar Epithelial Cells
title_sort effects of different ligands in the notch signaling pathway on the proliferation and transdifferentiation of primary type ii alveolar epithelial cells
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424003/
https://www.ncbi.nlm.nih.gov/pubmed/32850559
http://dx.doi.org/10.3389/fped.2020.00452
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