Lumican Peptides: Rational Design Targeting ALK5/TGFBRI

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dc.citation.volume7
dc.contributor.authorGesteira, Tarsis Ferreira
dc.contributor.authorCoulson-Thomas, Vivien J.
dc.contributor.authorYuan, Yong
dc.contributor.authorZhang, Jianhua
dc.contributor.authorNader, Helena B. [UNIFESP]
dc.contributor.authorKao, Winston W. -Y.
dc.coverageLondon
dc.date.accessioned2020-07-17T14:02:58Z
dc.date.available2020-07-17T14:02:58Z
dc.date.issued2017
dc.description.abstractLumican, a small leucine rich proteoglycan (SLRP), is a component of extracellular matrix which also functions as a matrikine regulating multiple cell activities. In the cornea, lumican maintains corneal transparency by regulating collagen fibrillogenesis, promoting corneal epithelial wound healing, regulating gene expression and maintaining corneal homeostasis. We have recently shown that a peptide designed from the 13 C-terminal amino acids of lumican (LumC13) binds to ALK5/TGFBR1 (type1 receptor of TGF beta) to promote wound healing. Herein we evaluate the mechanism by which this synthetic C-terminal amphiphilic peptide (LumC13), binds to ALK5. These studies clearly reveal that LumC13-ALK5 form a stable complex. In order to determine the minimal amino acids required for the formation of a stable lumican/ALK5 complex derivatives of LumC13 were designed and their binding to ALK5 investigated in silico. These LumC13 derivatives were tested both in vitro and in vivo to evaluate their ability to promote corneal epithelial cell migration and corneal wound healing, respectively. These validations add to the therapeutic value of LumC13 (Lumikine) and aid its clinical relevance of promoting the healing of corneal epithelium debridement. Moreover, our data validates the efficacy of our computational approach to design active peptides based on interactions of receptor and chemokine/ligand.en
dc.description.affiliationUniv Cincinnati, Dept Ophthalmol, Cincinnati, OH 45267 USA
dc.description.affiliationUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, Brazil
dc.description.affiliationUniv Houston, Coll Optometry, Ocular Surface Inst, Houston, TX 77204 USA
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNIH/NEI grants
dc.description.sponsorshipResearch to Prevent Blindness
dc.description.sponsorshipOhio Eye Research Foundation
dc.description.sponsorshipIDNIH/NEI grants: RO1 EY011845
dc.description.sponsorshipIDNIH/NEI grants: R01 021768
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1038/srep42057
dc.identifier.citationScientific Reports. London, v. 7, p. -, 2017.
dc.identifier.doi10.1038/srep42057
dc.identifier.fileWOS000393693200001.pdf
dc.identifier.issn2045-2322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55111
dc.identifier.wosWOS:000393693200001
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofScientific Reports
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleLumican Peptides: Rational Design Targeting ALK5/TGFBRIen
dc.typeinfo:eu-repo/semantics/article
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