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| Content Provider | Springer Nature Link |
|---|---|
| Author | Li, Shuangshuang Yang, Guangdong |
| Copyright Year | 2015 |
| Abstract | The gasotransmitter role of H$_{2}$S in mammalian has been extensively studied, and cystathionine gamma-lyase (CSE) is the major H$_{2}$S-producing enzyme in vascular system. Dysregulation of CSE/H$_{2}$S system was found in various pathophysiological conditions. MicroRNA (miRNA) and short interfering RNA (siRNA) are known to inhibit gene expression by mRNA degradation and/or translation repression. The regulation of CSE expression by miRNA and siRNA has been reported recently, but the off-target effect of miRNA and the lower knockdown efficiency of siRNA have shadowed the application of these approaches. In the present study, we designed CSE-specific miRNAs based on the rules of miRNA–mRNA complementary and human CSE cDNA sequence. The CSE-specific miRNAs significantly inhibited CSE expression and H$_{2}$S production, increased reactive oxygen species generation, and induced proliferation of human aorta smooth muscle cells (HASMCs). The designed CSE-specific miRNAs specifically targeted on CSE gene as evidenced by the direct inhibition of luciferase activity from reporter gene containing human CSE 3′-UTR sequence. The expression of other genes, such as estrogen receptor α, heme oxygenase 1, specificity protein 1, and 3-mercaptopyruvate sulfurtransferase, was not affected by the CSE-specific miRNAs. Compared with CSE-siRNAs, CSE-specific miRNAs displayed significantly higher efficacy in suppressing CSE expression and H$_{2}$S production. miR-143, a highly expressed miRNA in vascular system, down-regulated the expressions of CSE as well as other genes, such as insulin-like growth factor binding protein 5 and kruppel-like factor 4. miR-143 suppressed H$_{2}$S production but had no effect on HASMC proliferation. In conclusion, CSE-specific miRNAs designed in our study provide a highly effective research tool for regulating CSE expression and H$_{2}$S production. These CSE-specific miRNAs have potential as being novel therapeutic agents for treating vascular disorders related to abnormal oxidative stress and SMC growth. |
| Starting Page | 503 |
| Ending Page | 510 |
| Page Count | 8 |
| File Format | |
| ISSN | 20959273 |
| Journal | Chinese Science Bulletin |
| Volume Number | 60 |
| Issue Number | 5 |
| e-ISSN | 20959281 |
| Language | English |
| Publisher | Science China Press |
| Publisher Date | 2015-02-15 |
| Publisher Place | Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | H$_{2}$S Cystathionine gamma-lyase MicroRNAs siRNA Smooth muscle cells Science Life Sciences Physics Chemistry/Food Science Earth Sciences Engineering |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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