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Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts

Fibroblast growth factor (FGF) signaling is necessary for proper lung branching morphogenesis, alveolarization, and vascular development. Dysregulation of FGF activity has been implicated in various lung diseases. Recently, we showed that FGF18 promotes human lung branching morphogenesis by regulati...

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Autores principales: Belgacemi, Randa, Cherry, Caroline, El Alam, Imad, Frauenpreis, Andrew, Glass, Ian, Bellusci, Saverio, Danopoulos, Soula, Al Alam, Denise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493313/
https://www.ncbi.nlm.nih.gov/pubmed/37701781
http://dx.doi.org/10.3389/fcell.2023.1220002
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author Belgacemi, Randa
Cherry, Caroline
El Alam, Imad
Frauenpreis, Andrew
Glass, Ian
Bellusci, Saverio
Danopoulos, Soula
Al Alam, Denise
author_facet Belgacemi, Randa
Cherry, Caroline
El Alam, Imad
Frauenpreis, Andrew
Glass, Ian
Bellusci, Saverio
Danopoulos, Soula
Al Alam, Denise
author_sort Belgacemi, Randa
collection PubMed
description Fibroblast growth factor (FGF) signaling is necessary for proper lung branching morphogenesis, alveolarization, and vascular development. Dysregulation of FGF activity has been implicated in various lung diseases. Recently, we showed that FGF18 promotes human lung branching morphogenesis by regulating mesenchymal progenitor cells. However, the underlying mechanisms remain unclear. Thus, we aimed to determine the role of FGF18 and its receptors (FGFR) in regulating mesenchymal cell proliferation, migration, and differentiation from pseudoglandular to canalicular stage. We performed siRNA assays to identify the specific FGFR(s) associated with FGF18-induced biological processes. We found that FGF18 increased proliferation and migration in human fetal lung fibroblasts (HFLF) from both stages. FGFR2/FGFR4 played a significant role in pseudoglandular stage. HFLF proliferation, while FGFR3/FGFR4 were involved in canalicular stage. FGF18 enhanced HFLF migration through FGFR2 and FGFR4 in pseudoglandular and canalicular stage, respectively. Finally, we provide evidence that FGF18 treatment leads to reduced expression of myofibroblast markers (ACTA2 and COL1A1) and increased expression of lipofibroblast markers (ADRP and PPARγ) in both stages HFLF. However, the specific FGF18/FGFR complex involved in this process varies depending on the stage. Our findings suggest that in context of human lung development, FGF18 tends to associate with distinct FGFRs to initiate specific biological processes on mesenchymal cells.
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spelling pubmed-104933132023-09-12 Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts Belgacemi, Randa Cherry, Caroline El Alam, Imad Frauenpreis, Andrew Glass, Ian Bellusci, Saverio Danopoulos, Soula Al Alam, Denise Front Cell Dev Biol Cell and Developmental Biology Fibroblast growth factor (FGF) signaling is necessary for proper lung branching morphogenesis, alveolarization, and vascular development. Dysregulation of FGF activity has been implicated in various lung diseases. Recently, we showed that FGF18 promotes human lung branching morphogenesis by regulating mesenchymal progenitor cells. However, the underlying mechanisms remain unclear. Thus, we aimed to determine the role of FGF18 and its receptors (FGFR) in regulating mesenchymal cell proliferation, migration, and differentiation from pseudoglandular to canalicular stage. We performed siRNA assays to identify the specific FGFR(s) associated with FGF18-induced biological processes. We found that FGF18 increased proliferation and migration in human fetal lung fibroblasts (HFLF) from both stages. FGFR2/FGFR4 played a significant role in pseudoglandular stage. HFLF proliferation, while FGFR3/FGFR4 were involved in canalicular stage. FGF18 enhanced HFLF migration through FGFR2 and FGFR4 in pseudoglandular and canalicular stage, respectively. Finally, we provide evidence that FGF18 treatment leads to reduced expression of myofibroblast markers (ACTA2 and COL1A1) and increased expression of lipofibroblast markers (ADRP and PPARγ) in both stages HFLF. However, the specific FGF18/FGFR complex involved in this process varies depending on the stage. Our findings suggest that in context of human lung development, FGF18 tends to associate with distinct FGFRs to initiate specific biological processes on mesenchymal cells. Frontiers Media S.A. 2023-08-28 /pmc/articles/PMC10493313/ /pubmed/37701781 http://dx.doi.org/10.3389/fcell.2023.1220002 Text en Copyright © 2023 Belgacemi, Cherry, El Alam, Frauenpreis, Glass, Bellusci, Danopoulos and Al Alam. https://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 Cell and Developmental Biology
Belgacemi, Randa
Cherry, Caroline
El Alam, Imad
Frauenpreis, Andrew
Glass, Ian
Bellusci, Saverio
Danopoulos, Soula
Al Alam, Denise
Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts
title Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts
title_full Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts
title_fullStr Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts
title_full_unstemmed Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts
title_short Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts
title_sort preferential fgf18/fgfr activity in pseudoglandular versus canalicular stage human lung fibroblasts
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493313/
https://www.ncbi.nlm.nih.gov/pubmed/37701781
http://dx.doi.org/10.3389/fcell.2023.1220002
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