|
| Status |
Public on Oct 17, 2019 |
| Title |
MicroRNA-7a overexpression in VMH restores the sympathoadrenal response to hypoglycemia |
| Organism |
Rattus norvegicus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
It is proposed that the impaired sympathoadrenal response to hypoglycemia induced by recurrent insulin-induced hypoglycemia (RH) is an adaptive phenomenon induced by specific changes in microRNA expression in the ventromedial hypothalamus (VMH). To test this hypothesis, genome-wide microRNAomic profiling of the VMH by RNA-sequencing was performed in control and RH treated rats. Differential expression analysis identified microRNA-7a-5p and microRNA-665 as potential mediators of this phenomenon. To further test this hypothesis, experiments were conducted consisting of targeted lentiviral-mediated overexpression of microRNA-7a-5p and downregulation of microRNA-665 in the VMH. Hyperinsulinemic hypoglycemic clamp experiments demonstrated that targeted overexpression of microRNA-7a-5p (but not downregulation of microRNA-665) in the VMH of RH rats restored the epinephrine response to hypoglycemia. This restored response to hypoglycemia was associated with a restoration of GABAA receptor gene expression. Finally, a direct interaction of microRNA-7a-5p with 3’-UTR of GABAA receptor α1-subunit (Gabra1) gene was demonstrated in a luciferase assay. These findings indicate that 1) the impaired sympathoadrenal response induced by RH is associated with changes in VMH microRNA expression, and 2) microRNA-7a-5p, possibly via direct downregulation of GABA receptor gene expression, may serve as a mediator of the altered sympathoadrenal response to hypoglycemia.
|
| |
|
| Overall design |
12 samples were analysed (6 from each group).
|
| |
|
| Contributor(s) |
Agrawal R, Fisher SJ |
| Citation(s) |
31619588 |
| Submission date |
Oct 06, 2019 |
| Last update date |
Jan 16, 2020 |
| Contact name |
Rahul Agrawal |
| Organization name |
University of Utah
|
| Lab |
Fisher's Lab
|
| Street address |
15 N 2030 E
|
| City |
Salt Lake City |
| State/province |
UTAH |
| ZIP/Postal code |
84112 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA576074 |
| SRA |
SRP224541 |
Less...
More...