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Caracterização de duas linhas de peixe-zebra mutantes para a elastina no estudo da síndrome de Keutel
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Abstract(s)
É essencial que haja um equilíbrio nos processos metabólicos envolvidos no ciclo de
remodelação óssea, para que tenhamos um correto e dinâmico funcionamento do sistema
musculoesquelético, evitando assim possíveis patologias.
A síndrome de Keutel é uma doença autossómica recessiva rara que está associada a
uma mutação específica. O gene afetado codifica a proteína Gla da matriz (MGP), um
componente da matriz extracelular. Esta patologia envolve uma alteração de fenótipo e é
principalmente caracterizada pela presença de um excesso de calcificação, como
resultado de causas genéticas e defeitos bioquímicos. De forma geral, podemos dizer que
mutações associadas ao gene da MGP resultam em proteínas alteradas e/ou disfuncionais,
responsáveis pelo desenvolvimento de alterações patológicas.
Um outro importante constituinte da matriz extracelular são as fibras elásticas.
Constituídas essencialmente por elastina, uma proteína estrutural, podem ser encontradas
em tecidos moles, na traqueia, laringe, pavilhão auricular, pele, tendões e cartilagem. A
sua principal função é fornecer elasticidade e resistência a tecidos dinâmicos, como os
pulmões e as artérias.
Estudos sugerem a existência de uma interligação positiva entre a mineralização
anormal, provocada pela presença de MGP mutada, e a degradação de elastina. Assim,
foi do nosso interesse investigar a interação entre estas duas proteínas, através da
caracterização de duas linhas de peixe-zebra mutantes para a elastina. Por recurso à
análise fenotípica, viabilidade reprodutiva, exposição a antagonistas da vitamina K,
análise histológica e imunohistoquímica, conseguimos obter alguns resultados que
apoiam a hipótese de uma associação entre a existência de uma MGP disfuncional e a
consequente degradação de fibras elásticas.
It is essential that there is a balance in the processes involved in the bone remodeling cycle so that we have a good and dynamic functioning of the musculoskeletal system, thus avoiding possible pathologies. Keutel’s syndrome is a rare autosomal recessive disease that is associated with a specific mutation. The affected gene encodes the matrix Gla protein (MGP), an extracellular matrix protein. This pathology involves a change of phenotype and is mainly characterized by the presence of excessive calcification as a result of genetic causes and biochemical defects. In general, we can say that mutations associated with the MGP gene result in altered and/or dysfunctional proteins, thus leading to the development of disease. Another important component of the extracellular matrix is the elastic fibers. These fibers are made up essentially of elastin, a structural protein, and they can be found in soft tissues, trachea, larynx, pinna, skin, tendons, and cartilage. Their main function is to provide elasticity and resistance to dynamic tissues such as the lungs and arteries. Studies suggest the existence of a positive interconnection between abnormal mineralization, caused by a mutation in MGP, and the degradation of elastin. Thus, it was of our interest to investigate the interaction between these two proteins, through the characterization of two zebrafish mutant lines for elastin. By using phenotypic analysis, reproductive viability, exposure to vitamin K antagonists, histological and immunohistochemical analysis, we were able to obtain some results that indicate a possible association between a dysfunctional MGP and the consequent degradation of elastic fibers.
It is essential that there is a balance in the processes involved in the bone remodeling cycle so that we have a good and dynamic functioning of the musculoskeletal system, thus avoiding possible pathologies. Keutel’s syndrome is a rare autosomal recessive disease that is associated with a specific mutation. The affected gene encodes the matrix Gla protein (MGP), an extracellular matrix protein. This pathology involves a change of phenotype and is mainly characterized by the presence of excessive calcification as a result of genetic causes and biochemical defects. In general, we can say that mutations associated with the MGP gene result in altered and/or dysfunctional proteins, thus leading to the development of disease. Another important component of the extracellular matrix is the elastic fibers. These fibers are made up essentially of elastin, a structural protein, and they can be found in soft tissues, trachea, larynx, pinna, skin, tendons, and cartilage. Their main function is to provide elasticity and resistance to dynamic tissues such as the lungs and arteries. Studies suggest the existence of a positive interconnection between abnormal mineralization, caused by a mutation in MGP, and the degradation of elastin. Thus, it was of our interest to investigate the interaction between these two proteins, through the characterization of two zebrafish mutant lines for elastin. By using phenotypic analysis, reproductive viability, exposure to vitamin K antagonists, histological and immunohistochemical analysis, we were able to obtain some results that indicate a possible association between a dysfunctional MGP and the consequent degradation of elastic fibers.
Description
Keywords
Síndrome de Keutel MGP Calcificação Elastina Mutantes