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Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation
Koehler, Linda ;  Samsonov, Sergey ;  Rother, Sandra ;  Vogel, Sarah ;  Koehling, Sebastian ;  Moeller, Stephanie ;  Rademann, Joerg

HaupttitelSulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation
TitelzusatzPossible Consequences for TGF-β1 Signaling
AutorKoehler, Linda
AutorSamsonov, Sergey
AutorRother, Sandra
AutorVogel, Sarah
AutorKoehling, Sebastian
AutorMoeller, Stephanie
AutorRademann, Joerg
Seitenzahl21 S.
Freie SchlagwörterGrowth factor signalling; Molecular modelling; Polysaccharides
DDC615 Pharmakologie, Therapie
540 Chemie
Auch erschienen inScientific Reports. - 7 (2017), Artikel Nr. 1210
ZusammenfassungGlycosaminoglycans 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.
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Fachbereich/EinrichtungFB Biologie, Chemie, Pharmazie
Erscheinungsjahr2017
Dokumententyp/-SammlungenWissenschaftlicher Artikel
SpracheEnglisch
RechteCreative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Anmerkungen des AutorsDer Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
Erstellt am19.05.2017 - 10:03:39
Letzte Änderung19.05.2017 - 10:13:57
 
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000027036
DOI10.1038/s41598-017-01264-8
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