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Overexpression of microRNA-183 promotes apoptosis of substantia nigra neurons via the inhibition of OSMR in a mouse model of Parkinson's disease.
- Source :
-
International journal of molecular medicine [Int J Mol Med] 2019 Jan; Vol. 43 (1), pp. 209-220. Date of Electronic Publication: 2018 Nov 07. - Publication Year :
- 2019
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Abstract
- The present study aimed to investigate the effect of microRNA‑183 (miR‑183) on substantia nigra neurons by targeting oncostatin M receptor (OSMR) in a mouse model of Parkinson's disease (PD). The positive expression rates of OSMR and the apoptosis of substantia nigra neurons were detected by immunohistochemistry and terminal deoxynucleotidyl transferase‑mediated dUTP‑biotin nick end‑labeling, respectively. Substantia nigra neurons in normal and PD mice were cultured in vitro. The association between miR‑183 and OSMR was verified using a dual luciferase reporter gene assay. The expression of miR‑183 and the phosphoinositide 3‑kinase‑Akt signaling pathway‑associated genes were detected by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. Cell apoptosis was detected by flow cytometry. OSMR is the target gene of miR‑183. The number of OSMR‑positive cells and the apoptotic rate of substantia nigra neurons were increased in the PD group. Neurons transfected with miR‑183 mimic exhibited elevated expression levels of miR‑183, B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax) and caspase‑9 and increased apoptotic rate, and reduced expression levels of OSMR, Akt, phosphorylated (p‑)Akt, glycogen synthase kinase‑3 (GSK‑3β), p‑GSK‑3β, Bcl‑2, insulin‑like growth factor 1 (IGF‑1), mammalian target of rapamycin (mTOR) and p‑mTOR. The miR‑183 inhibitor decreased the expression levels of miR‑183, Bax and caspase‑9 and the apoptotic rate; however, increased the expression of OSMR, Akt, p‑Akt, GSK‑3β, p‑GSK‑3β, Bcl‑2, IGF‑1, mTOR and p‑mTOR. The results of the present study provide evidence that the overexpression of miR‑183 promotes the apoptosis of substantia nigra neurons by inhibiting the expression of OSMR.
- Subjects :
- Animals
Base Sequence
Behavior, Animal
Caspase 9 metabolism
Disease Models, Animal
Insulin-Like Growth Factor I metabolism
Male
Mice, Inbred C57BL
MicroRNAs metabolism
Neurons metabolism
Proto-Oncogene Proteins c-akt metabolism
Receptors, Oncostatin M genetics
Receptors, Oncostatin M metabolism
TOR Serine-Threonine Kinases metabolism
bcl-2-Associated X Protein metabolism
Apoptosis genetics
MicroRNAs genetics
Neurons pathology
Parkinson Disease genetics
Receptors, Oncostatin M antagonists & inhibitors
Substantia Nigra pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-244X
- Volume :
- 43
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30431059
- Full Text :
- https://doi.org/10.3892/ijmm.2018.3982