Echinococcus multilocularis: Molecular characterization of EmSmadE, a novel BR-Smad involved in TGF-β and BMP signaling

Epping, Kerstin; Brehm, Klaus

doi:10.1016/j.exppara.2011.07.013

Cited by 13 publications

(22 citation statements)

References 45 publications

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“…Caenorhabditis elegans , E . multilocularis and Schistosome mansoni , a TGF-β family signaling pathway has been described 16 , 20 , 31 , 34 , 36 . Different processes were found to be regulated by the activation of this pathway in those parasites, such as body size, male tail development, embryo viability, and oocyte quality for C .…”

Section: Discussionmentioning

confidence: 99%

“…elegans ; 31 , 37 – 39 and regulation of developmental processes such as body axis formation or regeneration and parasite development for E . multilocularis 16 . For Schistosoma spp ., which have been widely studied, fully functional components of the TGF-β signaling pathway have been found expressed for a certain time in various life cycle stages, indicating that TGF-β is involved in a number of developmental processes throughout the parasite life cycle 40 , such as embryonic development, production of vitellocytes in female blood-flukes 6 , and mitotic activity 40 , organ development, cellular growth and proliferation 41 , and eggshell formation 42 .…”

Section: Discussionmentioning

confidence: 99%

“…TGFβ has been found expressed in brain granuloma cells from NC patients 12 , suggesting that this cytokine could be exerting immunomodulatory effects. In addition, it has been observed that some helminths have the potential to produce TGFβ family products (Activin and Bone morphogenetic protein) 6 , 13 – 15 and several of the TGFβ signaling pathways factors have been found in the genome of these parasites 16 . Overall, these findings suggest a relevant role for this growth factor in the host-parasite relationship.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Transforming Growth Factor-β upon Taenia solium and Taenia crassiceps Cysticerci

Adalid‐Peralta

Rosas

Arce-Sillas

et al. 2017

Sci Rep

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Taeniids exhibit a great adaptive plasticity, which facilitates their establishment, growth, and reproduction in a hostile inflammatory microenvironment. Transforming Growth Factor-β (TGFβ), a highly pleiotropic cytokine, plays a critical role in vertebrate morphogenesis, cell differentiation, reproduction, and immune suppression. TGFβ is secreted by host cells in sites lodging parasites. The role of TGFβ in the outcome of T. solium and T. crassiceps cysticercosis is herein explored. Homologues of the TGFβ family receptors (TsRI and TsRII) and several members of the TGFβ downstream signal transduction pathway were found in T. solium genome, and the expression of Type-I and -II TGFβ receptors was confirmed by RT-PCR. Antibodies against TGFβ family receptors recognized cysticercal proteins of the expected molecular weight as determined by Western blot, and different structures in the parasite external tegument. In vitro, TGFβ promoted the growth and reproduction of T. crassiceps cysticerci and the survival of T. solium cysticerci. High TGFβ levels were found in cerebrospinal fluid from untreated neurocysticercotic patients who eventually failed to respond to the treatment (P = 0.03) pointing to the involvement of TGFβ in parasite survival. These results indicate the relevance of TGFβ in the infection outcome by promoting cysticercus growth and treatment resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Transforming Growth Factor-β upon Taenia solium and Taenia crassiceps Cysticerci

Adalid‐Peralta

Rosas

Arce-Sillas

et al. 2017

Sci Rep

View full text Add to dashboard Cite

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“…Evidence for the association of the TGF-β/BMP signaling pathway with strobilation arose from the identification of two of its components, BMP2 and SMAD4, among the selected set of strobilation-related proteins. In metazoans, TGF-β/BMP signaling, including the BMP protein signal and the Smad family of transcription factors, regulates a wide variety of cellular processes, such as proliferation, differentiation, adhesion, migration, and apoptosis [34] and developmental events, such as body axis formation and regeneration [35]. Moreover, in E. granulosus, Smad4 transcription factor is expressed in the metacestode (cystic larval stage) and in protoscoleces in a tissue-specific manner, with the highest transcript levels being found in activated (strobilation-induced) protoscoleces [36].…”

Section: Discussionmentioning

confidence: 99%

Cestode strobilation: prediction of developmental genes and pathways

et al. 2020

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Background: Cestoda is a class of endoparasitic worms in the flatworm phylum (Platyhelminthes). During the course of their evolution cestodes have evolved some interesting aspects, such as their increased reproductive capacity. In this sense, they have serial repetition of their reproductive organs in the adult stage, which is often associated with external segmentation in a developmental process called strobilation. However, the molecular basis of strobilation is poorly understood. To assess this issue, an evolutionary comparative study among strobilated and non-strobilated flatworm species was conducted to identify genes and proteins related to the strobilation process. Results: We compared the genomic content of 10 parasitic platyhelminth species; five from cestode species, representing strobilated parasitic platyhelminths, and five from trematode species, representing non-strobilated parasitic platyhelminths. This dataset was used to identify 1813 genes with orthologues that are present in all cestode (strobilated) species, but absent from at least one trematode (non-strobilated) species. Developmentrelated genes, along with genes of unknown function (UF), were then selected based on their transcriptional profiles, resulting in a total of 34 genes that were differentially expressed between the larval (pre-strobilation) and adult (strobilated) stages in at least one cestode species. These 34 genes were then assumed to be strobilation related; they included 12 encoding proteins of known function, with 6 related to the Wnt, TGF-β/BMP, or G-protein coupled receptor signaling pathways; and 22 encoding UF proteins. In order to assign function to at least some of the UF genes/proteins, a global gene co-expression analysis was performed for the cestode species Echinococcus multilocularis. This resulted in eight UF genes/proteins being predicted as related to developmental, reproductive, vesicle transport, or signaling processes. Conclusions: Overall, the described in silico data provided evidence of the involvement of 34 genes/proteins and at least 3 developmental pathways in the cestode strobilation process. These results highlight on the molecular mechanisms and evolution of the cestode strobilation process, and point to several interesting proteins as potential developmental markers and/or targets for the development of novel antihelminthic drugs.

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“…Third, to cover Tgf-β, Bmp, and activin signaling that is for example involved in embryogenesis, apoptosis, cell differentiation, and/or cell growth (Horbelt et al 2012 ), we chose with eg-smadD an intracellular factor that acts downstream of the transmembrane receptors. SmadD is a co-Smad and was described for E. multilocularis earlier (Epping and Brehm 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Comparison of ex vivo harvested and in vitro cultured materials from Echinococcus granulosus by measuring expression levels of five genes putatively involved in the development and maturation of adult worms

et al. 2016

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Parts of the natural life cycle of Echinococcus granulosus can be retraced in vitro such as the development of protoscoleces into semiadult worms with three or more proglottids, or the redifferentiation of in vitro cultured protoscoleces into metacestode-like cystic structures. Most in vitro generated samples share—at the microscopical level—high similarities with those naturally grown, but developmental differences have also been documented, such as missing egg production in in vitro grown adults or unusual bladder/vesicle formation in protoscoleces cultured into the metacestode direction. The aim of the present study was to explore how far different in vitro generated stage-specific materials/structures match the natural situation on the transcriptome level, based on testing five exemplarily chosen different genes: the frizzled receptor eg-fz4 (posterior marker), the FGF receptor-like factor eg-fgfrl (anterior association), the cell differentiation protein eg-rcd1 (part of the CCR4-NOT complex, a key regulator of eukaryotic gene expression), the rapidly accelerated fibrosarcoma serin/threonin kinase eg-braf (part of the MAPK pathway involved, e.g., in EGF signaling) and the co-smad eg-smadD (downstream factor of TGFβ/BMP2/activin signaling). These genes—tested via qPCR—were selected such as to allow a discussion on their potential role in the development of E. granulosus into the adult stage. Thus, testing took place with three ex vivo isolated samples, namely (i) egg-containing adult worms, (ii) invaginated protoscoleces, and (iii) protoscolex-free germinal layer tissue. Respective data were compared (a) with in vitro generated metacestode-like microcysts developed from protoscolices, and (b) different development stages of protoscoleces in vitro cultured toward adult maturation. As a finding, only eg-smadD and partially eg-fz4 showed high expression similarities between ex vivo harvested and in vitro cultured E. granulosus, thus suggesting a putative role in adult maturation. Conclusively, the fact of using “only” five genes did not allow answering the question if ex vivo and in vitro materials are similar on the transcriptome level. Another experimental restriction arises from different growth conditions of the in vitro cultured materials, and comparing these to the ex vivo harvested ones. Future experiments may solve the problems by using fully standardized E. granulosus sample collection and fully standardized culture conditions.

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Echinococcus multilocularis: Molecular characterization of EmSmadE, a novel BR-Smad involved in TGF-β and BMP signaling

Cited by 13 publications

References 45 publications

Effect of Transforming Growth Factor-β upon Taenia solium and Taenia crassiceps Cysticerci

Effect of Transforming Growth Factor-β upon Taenia solium and Taenia crassiceps Cysticerci

Cestode strobilation: prediction of developmental genes and pathways

Comparison of ex vivo harvested and in vitro cultured materials from Echinococcus granulosus by measuring expression levels of five genes putatively involved in the development and maturation of adult worms

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