PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway

Abstract Cell-mediated contraction of collagenous matrices is modulated by various growth factors and cytokines, such as platelet-derived growth factor-BB (PDGF-BB). Here we used a genetic cell model to delineate defined signaling pathways that enhance collagen gel contraction downstream of ligand-s...

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Autores principales:	Vahid Reyhani, Maria Tsioumpekou, Tijs van Wieringen, Lars Rask, Johan Lennartsson, Kristofer Rubin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3bf7f0867e934afa8042fca5e704395d
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spelling	oai:doaj.org-article:3bf7f0867e934afa8042fca5e704395d2021-12-02T16:06:30ZPDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway10.1038/s41598-017-08411-12045-2322https://doaj.org/article/3bf7f0867e934afa8042fca5e704395d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08411-1https://doaj.org/toc/2045-2322Abstract Cell-mediated contraction of collagenous matrices is modulated by various growth factors and cytokines, such as platelet-derived growth factor-BB (PDGF-BB). Here we used a genetic cell model to delineate defined signaling pathways that enhance collagen gel contraction downstream of ligand-stimulated platelet-derived growth factor receptor-β (PDGF-Rβ). Our data show that PDGF BB-enhanced activations of phosphatidylinositol 3′-kinase (PI3K) and phospholipase Cγ (PLCγ) were necessary for PDGF-enhanced collagen gel contraction. Importantly, other defined signaling pathways down-stream of PDGF-Rβ were, however, dispensable. The decisive roles for PI3K and PLCγ were corroborated by experiments using selective inhibitors. Furthermore, we show that de-phosphorylation and thereby activation of cofilin that is important for the turnover of actin filaments, is depended on PI3K and PLCγ down-stream of PDGF-Rβ. Moreover, inhibition of protein kinase C (PKC) by GÖ6976 and bisindolylmaleimide-II abolished cofilin de-phosphorylation, as well as PDGF-enhanced contraction. In contrast, activation of the PKC protein family by 4β-phorbol 12-myristate 13-acetate (PMA) did not accelerate collagen gel contraction although it induced long-term cofilin de-phosphorylation, showing the need of a dynamic control of cofilin de-phosphorylation for PDGF-enhanced collagen gel contraction. Taken together, our data point to the involvement of a PI3K/PLCγ-PKC-cofilin pathway in both PDGF-enhanced cofilin de-phosphorylation and PDGF-enhanced collagen gel contraction.Vahid ReyhaniMaria TsioumpekouTijs van WieringenLars RaskJohan LennartssonKristofer RubinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vahid Reyhani Maria Tsioumpekou Tijs van Wieringen Lars Rask Johan Lennartsson Kristofer Rubin PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway
description	Abstract Cell-mediated contraction of collagenous matrices is modulated by various growth factors and cytokines, such as platelet-derived growth factor-BB (PDGF-BB). Here we used a genetic cell model to delineate defined signaling pathways that enhance collagen gel contraction downstream of ligand-stimulated platelet-derived growth factor receptor-β (PDGF-Rβ). Our data show that PDGF BB-enhanced activations of phosphatidylinositol 3′-kinase (PI3K) and phospholipase Cγ (PLCγ) were necessary for PDGF-enhanced collagen gel contraction. Importantly, other defined signaling pathways down-stream of PDGF-Rβ were, however, dispensable. The decisive roles for PI3K and PLCγ were corroborated by experiments using selective inhibitors. Furthermore, we show that de-phosphorylation and thereby activation of cofilin that is important for the turnover of actin filaments, is depended on PI3K and PLCγ down-stream of PDGF-Rβ. Moreover, inhibition of protein kinase C (PKC) by GÖ6976 and bisindolylmaleimide-II abolished cofilin de-phosphorylation, as well as PDGF-enhanced contraction. In contrast, activation of the PKC protein family by 4β-phorbol 12-myristate 13-acetate (PMA) did not accelerate collagen gel contraction although it induced long-term cofilin de-phosphorylation, showing the need of a dynamic control of cofilin de-phosphorylation for PDGF-enhanced collagen gel contraction. Taken together, our data point to the involvement of a PI3K/PLCγ-PKC-cofilin pathway in both PDGF-enhanced cofilin de-phosphorylation and PDGF-enhanced collagen gel contraction.
format	article
author	Vahid Reyhani Maria Tsioumpekou Tijs van Wieringen Lars Rask Johan Lennartsson Kristofer Rubin
author_facet	Vahid Reyhani Maria Tsioumpekou Tijs van Wieringen Lars Rask Johan Lennartsson Kristofer Rubin
author_sort	Vahid Reyhani
title	PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway
title_short	PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway
title_full	PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway
title_fullStr	PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway
title_full_unstemmed	PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway
title_sort	pdgf-bb enhances collagen gel contraction through a pi3k-plcγ-pkc-cofilin pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3bf7f0867e934afa8042fca5e704395d
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PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway

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