Regulation of Schistosoma mansoni Development and Reproduction by the Mitogen-Activated Protein Kinase Signaling Pathway

dc.creatorAndrade, Luiza Freire de
dc.creatorMourão, Marina de Moraes
dc.creatorGeraldo, Juliana Assis
dc.creatorCoelho, Fernanda Sales
dc.creatorSilva, Larissa Lopes
dc.creatorNeves, Renata Heisler
dc.creatorVolpini, Angela Cristina
dc.creatorSilva, José Roberto Machado
dc.creatorAraujo, Neusa
dc.creatorPimenta, Rafael Nacif
dc.creatorCaffrey, Conor R.
dc.creatorOliveira, Guilherme Corrêa de
dc.date2015-02-13T14:55:55Z
dc.date2015-02-13T14:55:55Z
dc.date2014
dc.date.accessioned2023-09-26T23:02:48Z
dc.date.available2023-09-26T23:02:48Z
dc.identifierANDRADE, Luiza Freire de et al. Regulation of Schistosoma mansoni Development and Reproduction by the Mitogen-Activated Protein Kinase Signaling Pathway. PLoS Neglected Tropical Diseases, v. 8, n. 6, p. 1-12, 2014.
dc.identifier1553-7366
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/9497
dc.identifier10.1371/journal.pntd.0002949
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8886215
dc.descriptionBACKGROUND: Protein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear. METHODOLOGY/PRINCIPAL FINDINGS: We employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade. CONCLUSIONS: We conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectSchistosoma mansoni
dc.subjectSchistosomiasis control
dc.subjectMAP kinases
dc.subjectMAPKs
dc.titleRegulation of Schistosoma mansoni Development and Reproduction by the Mitogen-Activated Protein Kinase Signaling Pathway
dc.typeArticle


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