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FTY720 induces cell cycle arrest and apoptosis of rat glomerular mesangial cells
Jingyu Jiang1, Xiaodong Huang, Yi Wang
1Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Shengli Street No. 26, Wuhan 430014, China. jjy1117@126.com
Abstract:
The present study aimed to examine the effect of FTY720, a new immunosuppressive agent, on the proliferation and apoptosis of glomerular mesangial cells (GMC), and investigate the underlying mechanisms. Cultured rat GMC were treated by FTY720, and the cell viability, apoptosis and cell cycle progression were examined. Furthermore, cell cycle related gene expression profile was analyzed by cDNA microarray, and the protein expression of cell cycle related genes as well as Bax and Bcl-2 were examined by Western blot. The results showed that FTY720 inhibited GMC proliferation and induced apoptosis of GMC in a dose- and time-dependent manner, and induced G(1) phase cell cycle arrest in GMC in a dose-dependent manner as well. cDNA microarray analysis revealed that FTY720 regulated the expression of cell cycle-related gene. Western blot analysis showed that FTY720 induced the downregulation of cyclin D1, cyclin E, CDK2, CDK4, Bcl-2 and E2F1 and the upregulation of Kip1/p27, Cip1/p21, Bax and Rb in GMC in a dose-dependent manner. These results demonstrated that FTY720 could inhibit the proliferation of GMC through inducing cell cycle arrest and apoptosis, probably via the regulation of the expression of cell cycle-related genes and Bax/Bcl-2.
Insights
FTY720, an immunosuppressive drug, was found to inhibit glomerular mesangial cell (GMC) proliferation and induce apoptosis. This occurs through cell cycle arrest and modulation of key cell cycle and apoptosis-related genes.
Area of Science:
- Nephrology
- Pharmacology
- Cell Biology
Background:
- Glomerular mesangial cells (GMCs) play a crucial role in kidney function.
- Understanding agents that modulate GMC behavior is vital for treating kidney diseases.
- FTY720 is a novel immunosuppressive agent with potential therapeutic applications.
Purpose of the Study:
- To investigate the effects of FTY720 on glomerular mesangial cell (GMC) proliferation and apoptosis.
- To elucidate the underlying molecular mechanisms of FTY720's action on GMCs.
- To examine FTY720's impact on cell cycle progression and gene expression.
Main Methods:
- Primary rat glomerular mesangial cells were cultured and treated with FTY720.
- Cell viability, apoptosis, and cell cycle progression assays were performed.
- Gene expression profiling was conducted using cDNA microarray.
- Protein expression levels were analyzed via Western blot for cell cycle regulators and apoptosis markers (Bax, Bcl-2).
Main Results:
- FTY720 demonstrated dose- and time-dependent inhibition of GMC proliferation and induction of apoptosis.
- FTY720 caused a dose-dependent G1 phase cell cycle arrest in GMCs.
- FTY720 modulated the expression of cell cycle-related genes, including downregulation of cyclin D1, cyclin E, CDK2, CDK4, Bcl-2, and E2F1, and upregulation of Kip1/p27, Cip1/p21, Bax, and Rb.
Conclusions:
- FTY720 effectively inhibits GMC proliferation and induces apoptosis.
- The mechanism involves cell cycle arrest at the G1 phase.
- FTY720 exerts its effects through regulating the expression of cell cycle-related genes and the Bax/Bcl-2 pathway.
