Lumican Peptides: Rational Design Targeting ALK5/TGFBRI
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/55111 http://dx.doi.org/10.1038/srep42057 |
Resumo: | Lumican, 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. |
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Gesteira, Tarsis FerreiraCoulson-Thomas, Vivien J.Yuan, YongZhang, JianhuaNader, Helena B. [UNIFESP]Kao, Winston W. -Y.2020-07-17T14:02:58Z2020-07-17T14:02:58Z2017Scientific Reports. London, v. 7, p. -, 2017.2045-2322https://repositorio.unifesp.br/handle/11600/55111http://dx.doi.org/10.1038/srep42057WOS000393693200001.pdf10.1038/srep42057WOS:000393693200001Lumican, 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.NIH/NEI grantsResearch to Prevent BlindnessOhio Eye Research FoundationUniv Cincinnati, Dept Ophthalmol, Cincinnati, OH 45267 USAUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, BrazilUniv Houston, Coll Optometry, Ocular Surface Inst, Houston, TX 77204 USAUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, BrazilNIH/NEI grants: RO1 EY011845NIH/NEI grants: R01 021768Web of Science-engNature Publishing GroupScientific ReportsLumican Peptides: Rational Design Targeting ALK5/TGFBRIinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLondon7info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000393693200001.pdfapplication/pdf1802478${dspace.ui.url}/bitstream/11600/55111/1/WOS000393693200001.pdf2cc63fb712e043f478d34087f7cc15ecMD51open accessTEXTWOS000393693200001.pdf.txtWOS000393693200001.pdf.txtExtracted texttext/plain57700${dspace.ui.url}/bitstream/11600/55111/2/WOS000393693200001.pdf.txt41eb8ea916f833dc240e2df1807e5102MD52open accessTHUMBNAILWOS000393693200001.pdf.jpgWOS000393693200001.pdf.jpgIM Thumbnailimage/jpeg7343${dspace.ui.url}/bitstream/11600/55111/4/WOS000393693200001.pdf.jpg762b47f489f3957b6c333c89c16136e6MD54open access11600/551112022-08-01 04:50:10.76open accessoai:repositorio.unifesp.br:11600/55111Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-08-01T07:50:10Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Lumican Peptides: Rational Design Targeting ALK5/TGFBRI |
title |
Lumican Peptides: Rational Design Targeting ALK5/TGFBRI |
spellingShingle |
Lumican Peptides: Rational Design Targeting ALK5/TGFBRI Gesteira, Tarsis Ferreira |
title_short |
Lumican Peptides: Rational Design Targeting ALK5/TGFBRI |
title_full |
Lumican Peptides: Rational Design Targeting ALK5/TGFBRI |
title_fullStr |
Lumican Peptides: Rational Design Targeting ALK5/TGFBRI |
title_full_unstemmed |
Lumican Peptides: Rational Design Targeting ALK5/TGFBRI |
title_sort |
Lumican Peptides: Rational Design Targeting ALK5/TGFBRI |
author |
Gesteira, Tarsis Ferreira |
author_facet |
Gesteira, Tarsis Ferreira Coulson-Thomas, Vivien J. Yuan, Yong Zhang, Jianhua Nader, Helena B. [UNIFESP] Kao, Winston W. -Y. |
author_role |
author |
author2 |
Coulson-Thomas, Vivien J. Yuan, Yong Zhang, Jianhua Nader, Helena B. [UNIFESP] Kao, Winston W. -Y. |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Gesteira, Tarsis Ferreira Coulson-Thomas, Vivien J. Yuan, Yong Zhang, Jianhua Nader, Helena B. [UNIFESP] Kao, Winston W. -Y. |
description |
Lumican, 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. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
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2020-07-17T14:02:58Z |
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Scientific Reports. London, v. 7, p. -, 2017. |
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https://repositorio.unifesp.br/handle/11600/55111 http://dx.doi.org/10.1038/srep42057 |
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2045-2322 |
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WOS000393693200001.pdf |
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10.1038/srep42057 |
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Scientific Reports. London, v. 7, p. -, 2017. 2045-2322 WOS000393693200001.pdf 10.1038/srep42057 WOS:000393693200001 |
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