Differential Gene Expression Profile Induced by Valproic Acid (VPA) in Pediatric Epileptic Patients.

Autor: Floriano-Sánchez E; Multidisciplinary Research Laboratory, Military Graduate School of Health, SEDENA, 11200 Mexico City, Mexico. florianoesa@hotmail.com., Brindis F; Multidisciplinary Research Laboratory, Military Graduate School of Health, SEDENA, 11200 Mexico City, Mexico. brindis77@unam.mx., Ortega-Cuellar D; Laboratory of Experimental Nutrition, National Institute of Pediatrics, 04530 Mexico City, Mexico. dortegadan@gmail.com., Ignacio-Mejía I; Multidisciplinary Research Laboratory, Military Graduate School of Health, SEDENA, 11200 Mexico City, Mexico. ivanignacio402@gmail.com., Moreno-Arriola E; Genetics Unit of Nutrition, Institute of Biomedical Research UNAM-National Institute of Pediatrics, 04530 Mexico City, Mexico. elizamor86@hotmail.com., Romero-Morelos P; Multidisciplinary Research Laboratory, Military Graduate School of Health, SEDENA, 11200 Mexico City, Mexico. pablo.r.morelos@gmail.com., Ceballos-Vasquez E; Multidisciplinary Research Laboratory, Military Graduate School of Health, SEDENA, 11200 Mexico City, Mexico. cevas0484@gmail.com., Córdova-Espinoza MG; Multidisciplinary Research Laboratory, Military Graduate School of Health, SEDENA, 11200 Mexico City, Mexico. mixtlipp@yahoo.com.mx.; Bacteriology Medical Laboratory, Microbiology Department, National School of Biological Sciences, National Polytechnic Institute, 11340 Mexico City, Mexico. mixtlipp@yahoo.com.mx., Arregoitia-Sarabia CK; Laboratory of Neurosciences, National Institute of Pediatrics, 04530 Mexico City, Mexico. cindy_arregoitia@hotmail.com.; Section of Research and Graduate Studies, National Polytechnic Institute, 11340 Mexico City, Mexico. cindy_arregoitia@hotmail.com., Sandoval-Pacheco R; Military Hospital of Specialties of Women and Neonatology, Service of Emergency, SEDENA, 11200 Mexico City, Mexico. drsandovalpacheco@hotmail.com., Carmona-Aparicio L; Laboratory of Neurosciences, National Institute of Pediatrics, 04530 Mexico City, Mexico. c_apariccio@yahoo.com.mx., Cárdenas-Rodríguez N; Laboratory of Neurosciences, National Institute of Pediatrics, 04530 Mexico City, Mexico. noemicr2001@yahoo.com.mx.
Jazyk: angličtina
Zdroj: Genes [Genes (Basel)] 2018 Jun 28; Vol. 9 (7). Date of Electronic Publication: 2018 Jun 28.
DOI: 10.3390/genes9070328
Abstrakt: Epilepsy is a neuronal disease that affects up to 70 million people worldwide. The development of effective therapies to combat childhood epilepsy requires early biomarkers. Here, we performed a whole-genome microarray analysis in blood cells to identify genes differentially expressed between epileptic and epileptic valproic acid (VPA)-treated children versus normal children to obtain information about the gene expression to help us to understand genetic aspects of this disease. We found that the most significant differentially expressed genes were related to the transcriptional factor cAMP-response element binding protein (CREB) that is overexpressed in children with epilepsy compared with normal children, and 6 and 12 months of VPA treatment reversed several of these changes. Interestingly, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), a type I transmembrane glycoprotein that binds collagen proteins and contains CREB binding sites, was one of the more up-regulated genes in epileptic patients, and treatment with VPA strongly reversed its up-regulation. CREB up-regulates genes related to epilepsy; here, we suggest that LAIR1 could activate CREB, and together, they trigger epilepsy. After VPA treatment, LAIR1 repressed genes by disrupting the functional LAIR1⁻CREB complex, resulting in successful treatment. A functional microarray analysis offers new information that could open novel avenues of research in biomarker discovery, which may be useful for the early identification of children with a predisposition to epilepsy.
Databáze: MEDLINE