[P1-3-47] Identification of a novel microRNA involving in apoptosis signaling
Keywords:microRNA、Apoptosis、Inflammation
[Background]It is well-known that in the obese state, there is mild chronic inflammation throughout the body. This chronic inflammation increases the production of chemokines such as MCP-1 from hypertrophied adipocytes, and obese humans and mice are markedly exposed to adipocyte apoptosis. microRNAs (miRNAs) are important regulators of biological activities, including apoptosis. Abnormalities in apoptosis contribute to the development of many diseases such as cancer. Therefore, it is believed that many diseases can be ameliorated if the expression of miRNAs can be regulated. The aim of this study is to discover miRNAs involved in apoptosis and to analyze their target genes.
[Materials & Methods] C57BL/6J wild type mice were fed a high-fat diet for 8 weeks to induce adipocyte apoptosis. The miRNAs with variable fluctuating expression were analyzed by microarray and confirmed by qPCR. We then searched for their putative target genes using target prediction sites. For several miRNAs of interest, we examined whether the expression of the target genes was suppressed or not using 3T3-L1 cells transfected with their miRNA mimics.
[Result & Conclusion] The microarray and qPCR analyses showed that the expression of miR-6402 is suppressed in inflamed adipocytes. Bone morphogenetic protein receptor type 2 (BMPR2) was a prediction target gene for miR-6402, and the gene and protein expression of BMPR2 were inhibited in 3T3-L1 cells transfected with a miR-6402 mimic. The stimulation of BMP4, a ligand for BMPR2, induced apoptosis in differentiated 3T3-L1 cells, but not in undifferentiated 3T3-L1 cells. In conclusion, miR-6402 targets the gene of BMPR2 to control apoptosis in adipose tissues.
[Materials & Methods] C57BL/6J wild type mice were fed a high-fat diet for 8 weeks to induce adipocyte apoptosis. The miRNAs with variable fluctuating expression were analyzed by microarray and confirmed by qPCR. We then searched for their putative target genes using target prediction sites. For several miRNAs of interest, we examined whether the expression of the target genes was suppressed or not using 3T3-L1 cells transfected with their miRNA mimics.
[Result & Conclusion] The microarray and qPCR analyses showed that the expression of miR-6402 is suppressed in inflamed adipocytes. Bone morphogenetic protein receptor type 2 (BMPR2) was a prediction target gene for miR-6402, and the gene and protein expression of BMPR2 were inhibited in 3T3-L1 cells transfected with a miR-6402 mimic. The stimulation of BMP4, a ligand for BMPR2, induced apoptosis in differentiated 3T3-L1 cells, but not in undifferentiated 3T3-L1 cells. In conclusion, miR-6402 targets the gene of BMPR2 to control apoptosis in adipose tissues.