dc.contributor.author
Koehler, Linda
dc.contributor.author
Samsonov, Sergey
dc.contributor.author
Rother, Sandra
dc.contributor.author
Vogel, Sarah
dc.contributor.author
Köhling, Sebastian
dc.contributor.author
Moeller, Stephanie
dc.contributor.author
Rademann, Jörg
dc.date.accessioned
2018-06-08T10:19:42Z
dc.date.available
2017-05-19T10:13:57.176Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20248
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-23553
dc.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.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Growth factor signalling
dc.subject
Molecular modelling
dc.subject
Polysaccharides
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie
dc.title
Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Scientific Reports. - 7 (2017), Artikel Nr. 1210
dc.title.subtitle
Possible Consequences for TGF-β1 Signaling
dcterms.bibliographicCitation.doi
10.1038/s41598-017-01264-8
dcterms.bibliographicCitation.url
http://www.nature.com/articles/s41598-017-01264-8
refubium.affiliation
Biologie, Chemie, Pharmazie
de
refubium.mycore.fudocsId
FUDOCS_document_000000027036
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000008216
dcterms.accessRights.openaire
open access