Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling

Abstract Glycosaminoglycans are known to bind biological mediators thereby modulating their biological activity. Sulfated hyaluronans (sHA) were reported to strongly interact with transforming growth factor (TGF)-β1 leading to impaired bioactivity in fibroblasts. The underlying mechanism is not full...

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Autores principales:	Linda Koehler, Sergey Samsonov, Sandra Rother, Sarah Vogel, Sebastian Köhling, Stephanie Moeller, Matthias Schnabelrauch, Jörg Rademann, Ute Hempel, M. Teresa Pisabarro, Dieter Scharnweber, Vera Hintze
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c04d4419433f40119e66c264da1ea33c
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spelling	oai:doaj.org-article:c04d4419433f40119e66c264da1ea33c2021-12-02T11:52:25ZSulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling10.1038/s41598-017-01264-82045-2322https://doaj.org/article/c04d4419433f40119e66c264da1ea33c2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01264-8https://doaj.org/toc/2045-2322Abstract Glycosaminoglycans are known to bind biological mediators thereby modulating their biological activity. Sulfated hyaluronans (sHA) were reported to strongly interact with transforming growth factor (TGF)-β1 leading to impaired bioactivity in fibroblasts. The underlying mechanism is not fully elucidated yet. Examining the interaction of all components of the TGF-β1:receptor complex with sHA by surface plasmon resonance, we could show that highly sulfated HA (sHA3) blocks binding of TGF-β1 to its TGF-β receptor-I (TβR-I) and -II (TβR-II). However, sequential addition of sHA3 to the TβR-II/TGF-β1 complex led to a significantly stronger recruitment of TβR-I compared to a complex lacking sHA3, indicating that the order of binding events is very important. Molecular modeling suggested a possible molecular mechanism in which sHA3 could potentially favor the association of TβR-I when added sequentially. For the first time bioactivity of TGF-β1 in conjunction with sHA was investigated at the receptor level. TβR-I and, furthermore, Smad2 phosphorylation were decreased in the presence of sHA3 indicating the formation of an inactive signaling complex. The results contribute to an improved understanding of the interference of sHA3 with TGF-β1:receptor complex formation and will help to further improve the design of functional biomaterials that interfere with TGF-β1-driven skin fibrosis.Linda KoehlerSergey SamsonovSandra RotherSarah VogelSebastian KöhlingStephanie MoellerMatthias SchnabelrauchJörg RademannUte HempelM. Teresa PisabarroDieter ScharnweberVera HintzeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Linda Koehler Sergey Samsonov Sandra Rother Sarah Vogel Sebastian Köhling Stephanie Moeller Matthias Schnabelrauch Jörg Rademann Ute Hempel M. Teresa Pisabarro Dieter Scharnweber Vera Hintze Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling
description	Abstract Glycosaminoglycans are known to bind biological mediators thereby modulating their biological activity. Sulfated hyaluronans (sHA) were reported to strongly interact with transforming growth factor (TGF)-β1 leading to impaired bioactivity in fibroblasts. The underlying mechanism is not fully elucidated yet. Examining the interaction of all components of the TGF-β1:receptor complex with sHA by surface plasmon resonance, we could show that highly sulfated HA (sHA3) blocks binding of TGF-β1 to its TGF-β receptor-I (TβR-I) and -II (TβR-II). However, sequential addition of sHA3 to the TβR-II/TGF-β1 complex led to a significantly stronger recruitment of TβR-I compared to a complex lacking sHA3, indicating that the order of binding events is very important. Molecular modeling suggested a possible molecular mechanism in which sHA3 could potentially favor the association of TβR-I when added sequentially. For the first time bioactivity of TGF-β1 in conjunction with sHA was investigated at the receptor level. TβR-I and, furthermore, Smad2 phosphorylation were decreased in the presence of sHA3 indicating the formation of an inactive signaling complex. The results contribute to an improved understanding of the interference of sHA3 with TGF-β1:receptor complex formation and will help to further improve the design of functional biomaterials that interfere with TGF-β1-driven skin fibrosis.
format	article
author	Linda Koehler Sergey Samsonov Sandra Rother Sarah Vogel Sebastian Köhling Stephanie Moeller Matthias Schnabelrauch Jörg Rademann Ute Hempel M. Teresa Pisabarro Dieter Scharnweber Vera Hintze
author_facet	Linda Koehler Sergey Samsonov Sandra Rother Sarah Vogel Sebastian Köhling Stephanie Moeller Matthias Schnabelrauch Jörg Rademann Ute Hempel M. Teresa Pisabarro Dieter Scharnweber Vera Hintze
author_sort	Linda Koehler
title	Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling
title_short	Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling
title_full	Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling
title_fullStr	Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling
title_full_unstemmed	Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling
title_sort	sulfated hyaluronan derivatives modulate tgf-β1:receptor complex formation: possible consequences for tgf-β1 signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c04d4419433f40119e66c264da1ea33c
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Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling

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