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2099-12-31
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THE METASTASIS-ASSOCIATED PROTEIN-1 GENE ENCODES A HOST PERMISSIVE FACTOR FOR SCHISTOSOMIASIS, A LEADING GLOBAL CAUSE OF INFLAMMATION AND CANCER
Hepato-biliary Malignancie
Hyperproliferation
Schistosoma haematobium
MTA-1
Author
Affilliation
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA / Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA / Departamento de Genética. Facultad de Medicina 11800. Universidad de la República. Montevideo, Uruguay.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA / Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA / Departamento de Genética. Facultad de Medicina 11800. Universidad de la República. Montevideo, Uruguay.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Department of Biochemistry and Molecular Biology, George Washington University Medical Center. Washington DC, USA.
Abstract
Schistosoma haematobium is responsible for two-thirds of the world’s 200-400 million cases of human schistosomiasis. It is a group 1 carcinogen and a leading cause of bladder cancer which occurs following years of chronic inflammation, fibrosis and hyper-proliferation in the host liver. The co-evolution of blood flukes of the genus Schistosoma and their human hosts is paradigmatic of long term parasite development, survival and maintenance in mammals. However, the contribution of host genes, especially those discrete from those of the immune system, necessary for parasite establishment and development remains poorly understood. The present study investigated the role of Metastasis-associated protein-1 gene (Mta1) product in the survival of S. haematobium. Significantly fewer S. haematobium worms and eggs were recovered from Mta1 ?/? than wild type mice. Comparative analysis of cytokine profiles indicated a loss of cytokine interdependence and aberrant Th1/Th2 cytokine response in the Mta1?/? mice compared to age-matched wild type mice. By utilizing this Mta1-null mouse model, we identified a distinct, contribution of the mammalian MTA1 in establishing a productive host-parasite interaction and thus revealed a host factor critical for the optimal survival of schistosomes and successful parasitism. Moreover, MTA1 appears to play a significant role in driving inflammatory responses to schistosome egg induced hepatic granulomata reactions, and thus offers a survival cue for parasitism as well as an obligatory contribution of liver in schistosomiasis. These findings raise the possibility to develop intervention strategies targeting MTA1 to reduce the global burden of schistosomiasis, inflammation and neoplasia.
Keywords
SchistosomiasisHepato-biliary Malignancie
Hyperproliferation
Schistosoma haematobium
MTA-1
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