RESUMO
Although extensive work has delineated many of the mechanisms of extracellular matrix (ECM) production, far less is known about pathways that regulate ECM degradation. This is particularly true of cellular internalization and degradation of matrix, which play an underappreciated role in ECM metabolism and lung fibrosis. For example, genetic perturbation of this pathway leads to exacerbated fibrosis in experimental animal models. In this work, we present the results of an unbiased screen of Drosophila phagocytes that yielded multiple genes that, when silenced, led to increased collagen uptake. We further describe the function of cell division cycle 7 kinase (CDC7) as a specific suppressor of collagen uptake. We show that the genetic or pharmacological inhibition of CDC7 results in increased expression of the collagen endocytic receptor Endo180. Chromobox 5 (CBX5) is a putative target of CDC7, and genetic silencing of CBX5 also results in increased Endo180 and collagen uptake. Finally, CRISPR-mediated activation of Endo180 expression results in increased collagen uptake, suggesting that CDC7 regulates collagen internalization through increased Endo180 expression. Targeting the regulatory elements of the collagen degradative machinery may be a useful therapeutic approach in diseases of fibrosis or malignancy.
Assuntos
Colágeno/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteólise , Animais , Linhagem Celular , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Colágeno/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Fibrose , Regulação Enzimológica da Expressão Gênica , Proteínas Serina-Treonina Quinases/genética , Receptores Mitogênicos/biossíntese , Receptores Mitogênicos/genéticaRESUMO
BACKGROUND: Neurocysticercosis is one of the most common causes of acquired epilepsy worldwide. Caused by Taenia solium, the infection uses pigs as an intermediate host and thus is often associated with proximity to and consumption of pigs. OBJECTIVE: This review explores the epidemiology of neurocysticercosis in endemic regions across Africa, Asia, and Latin America and examines common risk factors in these areas. METHODS: A literature review was conducted using pubmed to search for articles with key words including neurocysticercosis, Taenia, solium, epidemiology, and the names of countries and continents in the regions of interest. FINDINGS: Multiple risk factors for neurocysticercosis were identified, including inadequate regulation of pig farms and food safety, poor sanitation, and water contamination. In addition, additional barriers to appropriate diagnosis and management were found, including resource limitations and poor health literacy. CONCLUSION: Despite its global prevalence, effective limitation of neurocysticercosis is still achievable through projects which address common risk factors.