Effect of mitofusin 2 overexpression on the proliferation and apoptosis of high-glucose-induced rat glomerular mesangial cells
| Autor: | Tang Wan-Xin, Fu Ping, Wu Wei-Hua, Cui Tian-lei, Wang Ben |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
MAPK/ERK pathway
Time Factors Glomerular Mesangial Cell Cell Blotting Western Genetic Vectors Apoptosis Biology Real-Time Polymerase Chain Reaction Transfection Adenoviridae Cell Line GTP Phosphohydrolases Proliferating Cell Nuclear Antigen medicine Animals Diabetic Nephropathies Phosphorylation Extracellular Signal-Regulated MAP Kinases Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Cell growth Reverse Transcriptase Polymerase Chain Reaction Flow Cytometry Molecular biology Cell biology Rats Up-Regulation medicine.anatomical_structure Glucose Proto-Oncogene Proteins c-bcl-2 Nephrology Mesangial Cells Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Journal of nephrology. 25(6) |
| ISSN: | 1724-6059 |
| Popis: | Background: Mitofusin 2 (Mfn2) regulates mitochondrial morphology and associated signaling pathways. Howe- ver, the role of Mfn2 in kidney disease is not fully under- stood. The present study aimed to investigate the effects of Mfn2 overexpression on high-glucose-induced cell proliferation and apoptosis. Another objective was to explore the possible underlying signal transduction me- chanisms in a rat glomerular mesangial cell (GMC) line. Methods: After adenovirus-mediated Mfn2 gene tran- sfection, Mfn2 expression was detected by real-time PCR. Time-dependent concentration changes in Mfn2 and relevant proteins induced by high glucose were in- vestigated to define the optimal time for research. The protein expression levels of Mfn2, proliferating cell nu- clear antigen (PCNA), p-Akt, p-ERK1/2 and Bcl-2 were examined on Western blots. Cell proliferation was de- tected by the CCK-8 method. Apoptosis was analyzed by flow cytometry. Results: Mfn2 gene expression was successfully incre- ased via adenovirus mediation. The correlation of Mfn2 expression with p-ERK1/2 and phosphorylated Akt was significant 48 hours after high-glucose stimulation. p- ERK1/2 was increased by high glucose, but was inhibi- ted by overexpressed Mfn2. Changes in the PCNA and GMC proliferative level coincided with p-ERK1/2. Ove- rexpressed Mfn2 significantly inhibited Akt phosphory- lation and Bcl-2 expression. The apoptosis rate increa- sed in the AdMfn2 group. Conclusions: Overexpressed Mfn2 could alleviate GMC proliferation and increase apoptosis. Subsequently, cellular quantity is maintained, which may contribute to reversing early diabetic nephropathy pathological changes. Mfn2 may perform its activities through the MAPK/ERK and PI3K/Akt signal pathways in correla- tion with proliferation and apoptosis. |
| Databáze: | OpenAIRE |
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