Effect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatment

Detalhes bibliográficos
Autor(a) principal: Clarimundo, Vanessa Schuck
Data de Publicação: 2013
Tipo de documento: Trabalho de conclusão de curso
Idioma: eng
Título da fonte: Repositório Institucional da UFRGS
Texto Completo: http://hdl.handle.net/10183/152860
Resumo: Introduction: Gastrin-releasing peptide (GRP) is a functional homologue of bombesin, and its receptor signaling is involved in several functions, including inflammatory response. GRP and its receptor (GRPR) have been found in synovial membrane and fluid of rheumatoid arthritis patients. RC-3095 is an antagonist of GRPR. Objective: evaluate the role of gastrin-releasing peptide, its receptor and RC-3095 on fibroblast-like synovyocites (FLS) in RA development. Methods: Mouse DBA/1J FLS were isolated from the tarsus of the hind paws of collagen-induced arthritis. FLS immunocitochemistry was executed to evaluate the GRPR presence. Then, it was evaluated FLS viability treated with RC-3095 in 24 h and 48 h. After this, FLS proliferation stimulated with LPS or GRP was performed by MTT assay in 24h. Finally, invasion assay was realized in a transwell system using Matrigel-coated inserts and treated with GRP, RC-3095, GRP+RC-3095. Results: Immunocitochemistry confirmed the presence of GRPR in FLS and its antagonist was not cytotoxic for FLS. Any statistical difference was observed in proliferation assay. Although, in invasion assay GRP was able to increase FLS invasion and RC-3095 or GRP+RC-3095 treatment comparing with GRP was able to decrease FLS invasion. Conclusion: This is the first study to identify the presence of GRPR in FLS. GRP causes an increase in the FLS invasion and RC-3095 was able to reverse this effect. Therefore the interference on GRP pathway is a potential target for the treatment of rheumatoid arthritis using RC-3095 for future clinical trials.
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spelling Clarimundo, Vanessa SchuckXavier, Ricardo MachadoOliveira, Patricia Gnieslaw de2017-02-21T02:26:50Z2013http://hdl.handle.net/10183/152860000914657Introduction: Gastrin-releasing peptide (GRP) is a functional homologue of bombesin, and its receptor signaling is involved in several functions, including inflammatory response. GRP and its receptor (GRPR) have been found in synovial membrane and fluid of rheumatoid arthritis patients. RC-3095 is an antagonist of GRPR. Objective: evaluate the role of gastrin-releasing peptide, its receptor and RC-3095 on fibroblast-like synovyocites (FLS) in RA development. Methods: Mouse DBA/1J FLS were isolated from the tarsus of the hind paws of collagen-induced arthritis. FLS immunocitochemistry was executed to evaluate the GRPR presence. Then, it was evaluated FLS viability treated with RC-3095 in 24 h and 48 h. After this, FLS proliferation stimulated with LPS or GRP was performed by MTT assay in 24h. Finally, invasion assay was realized in a transwell system using Matrigel-coated inserts and treated with GRP, RC-3095, GRP+RC-3095. Results: Immunocitochemistry confirmed the presence of GRPR in FLS and its antagonist was not cytotoxic for FLS. Any statistical difference was observed in proliferation assay. Although, in invasion assay GRP was able to increase FLS invasion and RC-3095 or GRP+RC-3095 treatment comparing with GRP was able to decrease FLS invasion. Conclusion: This is the first study to identify the presence of GRPR in FLS. GRP causes an increase in the FLS invasion and RC-3095 was able to reverse this effect. Therefore the interference on GRP pathway is a potential target for the treatment of rheumatoid arthritis using RC-3095 for future clinical trials.application/pdfengArtrite reumatóidePeptídeo liberador de gastrinaGastrin-releasing peptide receptorRC-3095Fibroblasts like-synoviocyteRheumatoid arthritisTreatmentEffect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatmentinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisUniversidade Federal do Rio Grande do SulFaculdade de FarmáciaPorto Alegre, BR-RS2013Farmáciagraduaçãoinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL000914657.pdf000914657.pdfTexto completo (inglês)application/pdf444181http://www.lume.ufrgs.br/bitstream/10183/152860/1/000914657.pdff277f65f9c70b5180e40d551e7833f19MD51TEXT000914657.pdf.txt000914657.pdf.txtExtracted Texttext/plain37321http://www.lume.ufrgs.br/bitstream/10183/152860/2/000914657.pdf.txtd55d46222ba3d3e5ccbe511c0f33ed50MD5210183/1528602021-05-07 05:01:13.181397oai:www.lume.ufrgs.br:10183/152860Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-05-07T08:01:13Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false
dc.title.pt_BR.fl_str_mv Effect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatment
title Effect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatment
spellingShingle Effect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatment
Clarimundo, Vanessa Schuck
Artrite reumatóide
Peptídeo liberador de gastrina
Gastrin-releasing peptide receptor
RC-3095
Fibroblasts like-synoviocyte
Rheumatoid arthritis
Treatment
title_short Effect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatment
title_full Effect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatment
title_fullStr Effect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatment
title_full_unstemmed Effect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatment
title_sort Effect of rc-3095, an antagonist of gastrin-releasing peptide receptor, on fibroblast-like synovyocites : a potential new strategy for arthritis treatment
author Clarimundo, Vanessa Schuck
author_facet Clarimundo, Vanessa Schuck
author_role author
dc.contributor.author.fl_str_mv Clarimundo, Vanessa Schuck
dc.contributor.advisor1.fl_str_mv Xavier, Ricardo Machado
dc.contributor.advisor-co1.fl_str_mv Oliveira, Patricia Gnieslaw de
contributor_str_mv Xavier, Ricardo Machado
Oliveira, Patricia Gnieslaw de
dc.subject.por.fl_str_mv Artrite reumatóide
Peptídeo liberador de gastrina
topic Artrite reumatóide
Peptídeo liberador de gastrina
Gastrin-releasing peptide receptor
RC-3095
Fibroblasts like-synoviocyte
Rheumatoid arthritis
Treatment
dc.subject.eng.fl_str_mv Gastrin-releasing peptide receptor
RC-3095
Fibroblasts like-synoviocyte
Rheumatoid arthritis
Treatment
description Introduction: Gastrin-releasing peptide (GRP) is a functional homologue of bombesin, and its receptor signaling is involved in several functions, including inflammatory response. GRP and its receptor (GRPR) have been found in synovial membrane and fluid of rheumatoid arthritis patients. RC-3095 is an antagonist of GRPR. Objective: evaluate the role of gastrin-releasing peptide, its receptor and RC-3095 on fibroblast-like synovyocites (FLS) in RA development. Methods: Mouse DBA/1J FLS were isolated from the tarsus of the hind paws of collagen-induced arthritis. FLS immunocitochemistry was executed to evaluate the GRPR presence. Then, it was evaluated FLS viability treated with RC-3095 in 24 h and 48 h. After this, FLS proliferation stimulated with LPS or GRP was performed by MTT assay in 24h. Finally, invasion assay was realized in a transwell system using Matrigel-coated inserts and treated with GRP, RC-3095, GRP+RC-3095. Results: Immunocitochemistry confirmed the presence of GRPR in FLS and its antagonist was not cytotoxic for FLS. Any statistical difference was observed in proliferation assay. Although, in invasion assay GRP was able to increase FLS invasion and RC-3095 or GRP+RC-3095 treatment comparing with GRP was able to decrease FLS invasion. Conclusion: This is the first study to identify the presence of GRPR in FLS. GRP causes an increase in the FLS invasion and RC-3095 was able to reverse this effect. Therefore the interference on GRP pathway is a potential target for the treatment of rheumatoid arthritis using RC-3095 for future clinical trials.
publishDate 2013
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