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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-01264-8 |
| _version_ | 1818422017461846016 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T13:19:34Z |
| format | Article |
| id | doaj.art-c04d4419433f40119e66c264da1ea33c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:19:34Z |
| publishDate | 2017-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c04d4419433f40119e66c264da1ea33c2022-12-21T22:59:59ZengNature PortfolioScientific Reports2045-23222017-04-017111110.1038/s41598-017-01264-8Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 SignalingLinda Koehler0Sergey Samsonov1Sandra Rother2Sarah Vogel3Sebastian Köhling4Stephanie Moeller5Matthias Schnabelrauch6Jörg Rademann7Ute Hempel8M. Teresa Pisabarro9Dieter Scharnweber10Vera Hintze11Institute of Materials Science, Max Bergmann Center of Biomaterials, TU DresdenStructural Bioinformatics, BIOTEC TU DresdenInstitute of Materials Science, Max Bergmann Center of Biomaterials, TU DresdenMedical Department, Institute of Physiological Chemistry, TU DresdenInstitute of Pharmacy, Freie Universität BerlinBiomaterials Department, INNOVENT e.V.Biomaterials Department, INNOVENT e.V.Institute of Pharmacy, Freie Universität BerlinMedical Department, Institute of Physiological Chemistry, TU DresdenStructural Bioinformatics, BIOTEC TU DresdenInstitute of Materials Science, Max Bergmann Center of Biomaterials, TU DresdenInstitute of Materials Science, Max Bergmann Center of Biomaterials, TU DresdenAbstract 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.https://doi.org/10.1038/s41598-017-01264-8 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-01264-8 |
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