Project description:MicroRNAs (miRNAs) are 20–24 nt RNAs that can be packaged into exosomes and play important regulatory roles. Here we show that miRNA-containing exosomes from NK cells could alleviate symptoms of chronic mild stress in mice. In vivo experiment, these exosomes decreased the levels of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α in the medium of astrocytes. By microarray analysis of exosome miRNA profiles, miR-207 was found to be an overexpressed miRNA in exosomes derived from unstressed mice. Experiments confirmed that miR-207 directly targets TLR4 interactor with leucine-rich repeats (Tril) and inhibits NF-κB signaling downsream of TLRs in astrocytes. When overexpressed in astrocytes, miR-207 decreased the release of pro-inflammatory cytokines and by inclusion of miR-207 inhibitor in astrocytes, higher release of pro-inflammatory cytokines and higher expression of Tril was found in vitro experiments. When NK cells were transfected with miR-207 inhibitor, miR-207 levels in NK cells derived exosomes were also declined. These exosomes with low miR-207 levels showed a decreased antidepressant activity in the vivo experiment. Collectively, our findings revealed that exosomal miR-207 alleviated the depression symptoms of stress mice by targeting Tril to inhibit NF-κB signaling downstream of TLRs in astrocytes.
Project description:TMEM213, 207, 116, 72 and 30B were found to be deregulated in ccRCC tumors, but their function in the epithelium remains unclear. To obtain an insight into their role in cellular processes the five TMEM genes were overexpressed in HEK293 cell line
Project description:Group living animals must be able to express different behavior profiles depending on their social status. This implies that the same genotype may translate into different behavioral phenotypes through socially driven differential gene expression. Here we show for the first time that what triggers the switch between status-specific neurogenomic states is not the objective structure of the social interaction but rather the subjectsM-bM-^@M-^Y perception of its outcome. For this purpose we had male zebrafish fight either a real opponent or their own image on a mirror. Massive changes in the brain transcriptome were observed in real opponent fighters, which experience either a victory or a defeat. In contrast, mirror fighters, which had no information on fight outcome despite expressing aggressive behavior, failed to activate a neurogenomic response. These results indicate that, even in cognitively simple organisms such as zebrafish, neurogenomic responses underlying changes in social status rely on cognitive appraisal. Brain samples from zebrafish, Danio rerio were collected after experimental manipulations generated 4 phenotypes regarding social experience: mirror fighters (M), winners of a real opponent fight (W), losers of a real opponent fight (L); and socially isolated fish (I). After 30 minutes of experimental manipulation animals were anesthetized with a lethal dose of MS-222 (1000-1500 mg/l) and decapitated. Brains were rapidly collected, homogenized and RNA extracted following standard methods of RNeasy Lipid Tissue Mini Kit, Qiagen. RNA was then treated with DNase (RNase-free DNase set, Qiagen) to remove possible contaminations with genomic DNA and concentration and purity was estimated by spectrophotometric absorbance in a NanoDrop ND-1000 UV-Vis Spectrophotometer (Nano-Drop Technologies).