Down-regulation of miR-488 targeting to promote Jag1 expression inhibits hypoxia-reoxygenation myocardial H9c2 cell damage / 中华医学遗传学杂志

OBJECTIVE@#To study the effect of down-regulating miR-488 targeting Jag1 on the injury of hypoxia-reoxygenation myocardial H9c2 cells.@*METHODS@#A hypoxic-reoxygenated myocardial H9c2 cell injury model was constructed. miR-488 inhibitor was used to transfect the cells. CCK-8 method and flow cytometry were used to detect cell proliferation and apoptosis in each group. Lactate dehydrogenase (LDH), superoxide dismutase (SOD), malonaldehyde (MDA), catalase (CAT) levels were detected. Western blotting was used to detect the expression of Bcl-2 associated X Protein (Bax) and B cell lymphoma/lewkmia-2 (Bcl-2). Target genes of miR-488 were predicted, and a luciferase reporter system was used to verify the targeting relationship between the two. Myocardial H9c2 cells were co-transfected with miR-488 inhibitor and Jag1 siRNA, and treated with hypoxia and reoxygenation, cell proliferation, apoptosis, LDH, SOD, MDA, CAT levels, and Bax, Bcl-2 protein expression were detected.@*RESULTS@#The expression of miR-488 in the hypoxia-reoxygenated myocardial H9c2 cells was increased, along with reduced cell proliferation, increased apoptosis, increased Bax protein expression, decreased Bcl-2 protein expression, increased MDA, decreased CAT and SOD, and increased LDH level in the supernatant of cell culture. When myocardial H9c2 cells were transfected with miR-488 inhibitor and treated with hypoxia and reoxygenation, the expression of miR-488 was decreased, along with increased cell proliferation, decreased apoptosis, decreased Bax protein expression, increased Bcl-2 protein expression, decreased MDA, increased CAT and SOD, and decreased LDH level in the supernatant of cell culture. Down-regulation of miR-488 could target and down-regulate Jag1 expression. And Jag1 siRNA could reverse the effect of miR-488 inhibitor on the proliferation, apoptosis, LDH, SOD, MDA, CAT levels and the expression of Bax and Bcl-2 of hypoxic-reoxygenated myocardial H9c2 cells.@*CONCLUSION@#Down-regulating miR-488 targeted Jag1 can attenuate hypoxia-reoxygenation induced myocardial H9c2 cell injury.

Polimorfismos de los genes JAG1, MEF2C y BDNF asociados con la densidad mineral ósea en mujeres del norte de México / JAG1, MEF2C and BDNF polymorphisms associated with bone mineral density in women from Northern México

Resumen Introducción. La osteoporosis se caracteriza por una baja densidad mineral ósea; la composición genética es uno de los factores que más influyen en ella, pero hay pocos estudios de genes asociados con esta condición en la población mexicana. Objetivo. Investigar la posible asociación de ocho polimorfismos de un solo nucleótido (Single Nucleotide Polymorphism, SNP) de los genes JAG1, MEF2C y BDNF con la densidad mineral ósea en mujeres del norte de México. Materiales y métodos. Participaron 124 mujeres de 40 a 80 años, sin parentesco entre ellas. Su densidad mineral ósea se determinó mediante absorciometría dual de rayos X y la genotipificación se hizo utilizando discriminación alélica mediante PCR en tiempo real; se estudiaron cuatro de los SNP del gen JAG1 (rs6514116, rs2273061, rs2235811 y rs6040061), tres del MEF2C (rs1366594, rs12521522 y rs11951031) y uno del BDNF (rs6265). El análisis estadístico de los datos obtenidos se hizo por regresión lineal. Resultados. El SNP rs2235811 presentó asociación significativa con la densidad mineral ósea de todo el cuerpo bajo el modelo de herencia dominante (p=0,024) y, aunque los otros SNP no tuvieron relación significativa con esta densidad, en ninguno de los modelos de herencia estudiados, se observó una tendencia hacia esta asociación. Conclusión. Los resultados sugieren que el SNP rs2235811 del gen JAG1 podría contribuir a la variación en la densidad mineral ósea de las mujeres del norte de México.

Abstract Introduction: Osteoporosis is characterized by a low bone mineral density. Genetic composition is one of the most influential factors in determining bone mineral density (BMD). There are few studies on genes associated with BMD in the Mexican population. Objective: To investigate the association of eight single nucleotide polymorphisms (SNP) of JAG1, MEF2C and BDNF genes with BMD in women of Northern México. Materials and methods: This study involved 124 unrelated Mexican women between 40 and 80 years old. BMD was determined by dual X-ray absorptiometry. Genotyping was performed using allelic discrimination by real time PCR. We analyzed the SNP of JAG1 (rs6514116, rs2273061, rs2235811 and rs6040061), MEF2C (rs1366594, rs12521522 and rs11951031), and BDNF (rs6265) and the data using linear regression. Results: The JAG1 SNP rs2235811 was associated with the BMD of the total body under the dominant inheritance model (p=0,024). Although the other SNPs were not associated with BMD in any of the inheritance models studied, a trend was observed. Conclusion: Our results suggest that the SNP rs2235811 in the JAG1 gene might contribute to the variation in BMD in women from northern México.