Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected i...

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Main Authors: Simona Ceccarelli, Cristina Nodale, Enrica Vescarelli, Paola Pontecorvi, Valeria Manganelli, Giovanni Casella, Maria Giuseppina Onesti, Maurizio Sorice, Ferdinando Romano, Antonio Angeloni, Cinzia Marchese
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/1075156
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author Simona Ceccarelli
Cristina Nodale
Enrica Vescarelli
Paola Pontecorvi
Valeria Manganelli
Giovanni Casella
Maria Giuseppina Onesti
Maurizio Sorice
Ferdinando Romano
Antonio Angeloni
Cinzia Marchese
author_facet Simona Ceccarelli
Cristina Nodale
Enrica Vescarelli
Paola Pontecorvi
Valeria Manganelli
Giovanni Casella
Maria Giuseppina Onesti
Maurizio Sorice
Ferdinando Romano
Antonio Angeloni
Cinzia Marchese
author_sort Simona Ceccarelli
collection DOAJ
description Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs.
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spelling doaj-art-7e0aa6a2f3874ee18dc50330cef62dda2025-02-03T06:42:29ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/10751561075156Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in AdipogenesisSimona Ceccarelli0Cristina Nodale1Enrica Vescarelli2Paola Pontecorvi3Valeria Manganelli4Giovanni Casella5Maria Giuseppina Onesti6Maurizio Sorice7Ferdinando Romano8Antonio Angeloni9Cinzia Marchese10Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, ItalyDepartment of Surgical Sciences, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, ItalyDepartment of Surgery “P. Valdoni”, Sapienza University of Rome, Viale del Policlinico 155, 00161 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Roma, ItalyAdipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs.http://dx.doi.org/10.1155/2018/1075156
spellingShingle Simona Ceccarelli
Cristina Nodale
Enrica Vescarelli
Paola Pontecorvi
Valeria Manganelli
Giovanni Casella
Maria Giuseppina Onesti
Maurizio Sorice
Ferdinando Romano
Antonio Angeloni
Cinzia Marchese
Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis
Stem Cells International
title Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis
title_full Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis
title_fullStr Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis
title_full_unstemmed Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis
title_short Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis
title_sort neuropilin 1 mediates keratinocyte growth factor signaling in adipose derived stem cells potential involvement in adipogenesis
url http://dx.doi.org/10.1155/2018/1075156
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