El papel de la FAK en la acantólisis del Pénfigo vulgar en un modelo murino
Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis, and autoantibodies against desmoglein 3 localized on desmosomes. In addition, caspases also seem to participate in this blistering disease. Focal adhesion kinase (FAK) is a non-receptor tyrosi...
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| Format: | info:eu-repo/semantics/doctoralThesis |
| Language: | spa |
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Servicio de Publicaciones de la Universidad de Navarra
2012
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| Online Access: | https://hdl.handle.net/10171/22532 |
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| author | Gil-Sanchez, M.P. (María Pilar) Lopez-Zabalza, M.J. (María Jesús) España, A. (Agustín) |
| author_facet | Gil-Sanchez, M.P. (María Pilar) Lopez-Zabalza, M.J. (María Jesús) España, A. (Agustín) |
| author_sort | Gil-Sanchez, M.P. (María Pilar) |
| collection | DSpace |
| description | Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis, and autoantibodies against desmoglein 3 localized on desmosomes. In addition, caspases also seem to participate in this blistering disease. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in cytoskeleton remodelling and formation and disassembly of cell adhesion structures. We have previously demonstrated that HER (human epidermal growth factor receptor related) isoforms, Src (Rous sarcoma) and mTOR (mammalian target of rapamycin), three molecules implicated in signalling processes, take part in suprabasal acantholysis and apoptosis induced by PV-IgG in a mouse model. Our aim was to investigate if upregulation of FAK is implicated in the development of PV lesions. Herein, using a mouse model, PV-IgG administration showed an increased level of FAK phosphorylated on 397 and 925 tyrosine residues in the basal layer of epidermis. When mice were pretreated with a FAK inhibitor the acantholysis of the basal layer of epidermis was absent. More interestingly, we observed that phosphorylated FAK (Y397/925) decreased when HER isoforms, Src, mTOR, and pan-caspases inhibitors were employed before PV-IgG administration. In addition, pretreatment with the FAK inhibitor before PV-IgG injection avoided the changes of both Bax and Bcl-2 expression and caspases-9 and –3 activities induced by PV-IgG. Finally, FAK inhibitor reduced expression of phosphorylated Src and mTOR in the basal cells of epidermis. In conclusion, our data reveal a novel biochemical mechanism for phosphorylated FAK (Y397/925) in PV development involving HER isoforms, Src and mTOR kinases. |
| format | info:eu-repo/semantics/doctoralThesis |
| id | oai:dadun.unav.edu:10171-22532 |
| institution | Universidad de Navarra |
| language | spa |
| publishDate | 2012 |
| publisher | Servicio de Publicaciones de la Universidad de Navarra |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-225322020-03-03T17:34:10Z El papel de la FAK en la acantólisis del Pénfigo vulgar en un modelo murino Gil-Sanchez, M.P. (María Pilar) Lopez-Zabalza, M.J. (María Jesús) España, A. (Agustín) Materias Investigacion::Ciencias de la Salud::Dermatología Modelo murino Acantólisis Pénfigo vulgar Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis, and autoantibodies against desmoglein 3 localized on desmosomes. In addition, caspases also seem to participate in this blistering disease. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in cytoskeleton remodelling and formation and disassembly of cell adhesion structures. We have previously demonstrated that HER (human epidermal growth factor receptor related) isoforms, Src (Rous sarcoma) and mTOR (mammalian target of rapamycin), three molecules implicated in signalling processes, take part in suprabasal acantholysis and apoptosis induced by PV-IgG in a mouse model. Our aim was to investigate if upregulation of FAK is implicated in the development of PV lesions. Herein, using a mouse model, PV-IgG administration showed an increased level of FAK phosphorylated on 397 and 925 tyrosine residues in the basal layer of epidermis. When mice were pretreated with a FAK inhibitor the acantholysis of the basal layer of epidermis was absent. More interestingly, we observed that phosphorylated FAK (Y397/925) decreased when HER isoforms, Src, mTOR, and pan-caspases inhibitors were employed before PV-IgG administration. In addition, pretreatment with the FAK inhibitor before PV-IgG injection avoided the changes of both Bax and Bcl-2 expression and caspases-9 and –3 activities induced by PV-IgG. Finally, FAK inhibitor reduced expression of phosphorylated Src and mTOR in the basal cells of epidermis. In conclusion, our data reveal a novel biochemical mechanism for phosphorylated FAK (Y397/925) in PV development involving HER isoforms, Src and mTOR kinases. 2012-06-11T09:59:12Z 2012-06-11T09:59:12Z 2012 2012-04-20 info:eu-repo/semantics/doctoralThesis https://hdl.handle.net/10171/22532 spa info:eu-repo/semantics/openAccess application/pdf Servicio de Publicaciones de la Universidad de Navarra |
| spellingShingle | Materias Investigacion::Ciencias de la Salud::Dermatología Modelo murino Acantólisis Pénfigo vulgar Gil-Sanchez, M.P. (María Pilar) Lopez-Zabalza, M.J. (María Jesús) España, A. (Agustín) El papel de la FAK en la acantólisis del Pénfigo vulgar en un modelo murino |
| title | El papel de la FAK en la acantólisis del Pénfigo vulgar en un modelo murino |
| title_full | El papel de la FAK en la acantólisis del Pénfigo vulgar en un modelo murino |
| title_fullStr | El papel de la FAK en la acantólisis del Pénfigo vulgar en un modelo murino |
| title_full_unstemmed | El papel de la FAK en la acantólisis del Pénfigo vulgar en un modelo murino |
| title_short | El papel de la FAK en la acantólisis del Pénfigo vulgar en un modelo murino |
| title_sort | el papel de la fak en la acantólisis del pénfigo vulgar en un modelo murino |
| topic | Materias Investigacion::Ciencias de la Salud::Dermatología Modelo murino Acantólisis Pénfigo vulgar |
| url | https://hdl.handle.net/10171/22532 |
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