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Effect of immunosuppression on the human mesangial cell cycle.

Zhou X, Workeneh B, Hu Z, Li R - Mol Med Rep (2014)

Bottom Line: Tac and CsA significantly inhibited the proliferation of human mesangial cells in a dose- and time-dependent manner.The combination of MP and MMF synergistically inhibited mesangial cell proliferation.In conclusion, these agents, sequentially or in combination, may be used to effectively treat mesangial proliferative glomerular disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Provincial People's Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

ABSTRACT
The present study investigated the effects of immunosuppressive agents [tacrolimus (Tac), cyclosporine A (CsA), mycophenolic acid (MMF) and methylprednisone (MP)] on the proliferation, cell cycle progression and apoptotic rate of human mesangial cells. Cultured human mesangial cells were treated with several concentrations of the immunosuppressive agents for 24, 48 or 72 h. Cell cycle progression, proliferation and apoptosis were analyzed using an MTT assay and flow cytometry. Tac and CsA significantly inhibited the proliferation of human mesangial cells in a dose- and time-dependent manner. Cell cycle analysis revealed that Tac and CsA arrested mesangial cells in the G0/G1 phase, preventing them from entering S phase. Similarly, MP inhibited human mesangial cell growth by causing cell cycle arrest in G0/G1 phase. MMF also inhibited mesangial cell proliferation, but accomplished this by preventing progression from S phase to the G2/M phase. The combination of MP and MMF synergistically inhibited mesangial cell proliferation. Tac, CsA, MP and MMF inhibited proliferation of human mesangial cells by blocking progression of the cell cycle. In conclusion, these agents, sequentially or in combination, may be used to effectively treat mesangial proliferative glomerular disease.

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CsA causes HMC growth arrest at the G0/G1 phase. (A) Quiescent HMCs were stimulated by 10% fetal calf serum with or without CsA (1 and 5 μmol/l) for 24, 48 and 72 h, and proliferation was examined by an MTT assay (*P<0.001 vs. 0 μmol/l ). (B–D) Representative flow cytometry results of HMC cycle analysis (control and CsA at 1 and 5 μmol/l for 48 h). (E) Statistical analysis results of B–D (*P<0.01 vs. 0 μmol/l). (F) HMCs were treated with CsA (1 and 5 μmol/l) for 48 h and apoptotic rates were measured by flow cytometry (*P<0.01 vs. 0 μmol/l). All values are presented as the mean ± standard deviation of three independent experiments. CsA, cyclosporine A; HMC, human mesangial cell.
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f2-mmr-11-02-0910: CsA causes HMC growth arrest at the G0/G1 phase. (A) Quiescent HMCs were stimulated by 10% fetal calf serum with or without CsA (1 and 5 μmol/l) for 24, 48 and 72 h, and proliferation was examined by an MTT assay (*P<0.001 vs. 0 μmol/l ). (B–D) Representative flow cytometry results of HMC cycle analysis (control and CsA at 1 and 5 μmol/l for 48 h). (E) Statistical analysis results of B–D (*P<0.01 vs. 0 μmol/l). (F) HMCs were treated with CsA (1 and 5 μmol/l) for 48 h and apoptotic rates were measured by flow cytometry (*P<0.01 vs. 0 μmol/l). All values are presented as the mean ± standard deviation of three independent experiments. CsA, cyclosporine A; HMC, human mesangial cell.

Mentions: As in the case of Tac, when human mesangial cells were exposed to CsA (1 and 5 μmol/l) in a dose- and time-dependent manner, cellular proliferation was inhibited (Fig. 2A). Following 48 h of exposure to CsA (1 and 5 μmol/l), the percentage of cells in S phase was significantly decreased and there was a significant increase in the percentage of cells in the G0/G1 phase (Fig. 2B–D). This indicated that CsA arrested human mesangial cells prior to their entry into S phase (Fig. 2E). Finally, the effects of CsA on apoptosis of human mesangial cells were assessed. When cells were exposed to CsA (1 and 5 μmol/l) for 48 h, the percentage of apoptotic cells significantly increased in a dose-dependent manner (Fig. 2F).


Effect of immunosuppression on the human mesangial cell cycle.

Zhou X, Workeneh B, Hu Z, Li R - Mol Med Rep (2014)

CsA causes HMC growth arrest at the G0/G1 phase. (A) Quiescent HMCs were stimulated by 10% fetal calf serum with or without CsA (1 and 5 μmol/l) for 24, 48 and 72 h, and proliferation was examined by an MTT assay (*P<0.001 vs. 0 μmol/l ). (B–D) Representative flow cytometry results of HMC cycle analysis (control and CsA at 1 and 5 μmol/l for 48 h). (E) Statistical analysis results of B–D (*P<0.01 vs. 0 μmol/l). (F) HMCs were treated with CsA (1 and 5 μmol/l) for 48 h and apoptotic rates were measured by flow cytometry (*P<0.01 vs. 0 μmol/l). All values are presented as the mean ± standard deviation of three independent experiments. CsA, cyclosporine A; HMC, human mesangial cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262500&req=5

f2-mmr-11-02-0910: CsA causes HMC growth arrest at the G0/G1 phase. (A) Quiescent HMCs were stimulated by 10% fetal calf serum with or without CsA (1 and 5 μmol/l) for 24, 48 and 72 h, and proliferation was examined by an MTT assay (*P<0.001 vs. 0 μmol/l ). (B–D) Representative flow cytometry results of HMC cycle analysis (control and CsA at 1 and 5 μmol/l for 48 h). (E) Statistical analysis results of B–D (*P<0.01 vs. 0 μmol/l). (F) HMCs were treated with CsA (1 and 5 μmol/l) for 48 h and apoptotic rates were measured by flow cytometry (*P<0.01 vs. 0 μmol/l). All values are presented as the mean ± standard deviation of three independent experiments. CsA, cyclosporine A; HMC, human mesangial cell.
Mentions: As in the case of Tac, when human mesangial cells were exposed to CsA (1 and 5 μmol/l) in a dose- and time-dependent manner, cellular proliferation was inhibited (Fig. 2A). Following 48 h of exposure to CsA (1 and 5 μmol/l), the percentage of cells in S phase was significantly decreased and there was a significant increase in the percentage of cells in the G0/G1 phase (Fig. 2B–D). This indicated that CsA arrested human mesangial cells prior to their entry into S phase (Fig. 2E). Finally, the effects of CsA on apoptosis of human mesangial cells were assessed. When cells were exposed to CsA (1 and 5 μmol/l) for 48 h, the percentage of apoptotic cells significantly increased in a dose-dependent manner (Fig. 2F).

Bottom Line: Tac and CsA significantly inhibited the proliferation of human mesangial cells in a dose- and time-dependent manner.The combination of MP and MMF synergistically inhibited mesangial cell proliferation.In conclusion, these agents, sequentially or in combination, may be used to effectively treat mesangial proliferative glomerular disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology, Provincial People's Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

ABSTRACT
The present study investigated the effects of immunosuppressive agents [tacrolimus (Tac), cyclosporine A (CsA), mycophenolic acid (MMF) and methylprednisone (MP)] on the proliferation, cell cycle progression and apoptotic rate of human mesangial cells. Cultured human mesangial cells were treated with several concentrations of the immunosuppressive agents for 24, 48 or 72 h. Cell cycle progression, proliferation and apoptosis were analyzed using an MTT assay and flow cytometry. Tac and CsA significantly inhibited the proliferation of human mesangial cells in a dose- and time-dependent manner. Cell cycle analysis revealed that Tac and CsA arrested mesangial cells in the G0/G1 phase, preventing them from entering S phase. Similarly, MP inhibited human mesangial cell growth by causing cell cycle arrest in G0/G1 phase. MMF also inhibited mesangial cell proliferation, but accomplished this by preventing progression from S phase to the G2/M phase. The combination of MP and MMF synergistically inhibited mesangial cell proliferation. Tac, CsA, MP and MMF inhibited proliferation of human mesangial cells by blocking progression of the cell cycle. In conclusion, these agents, sequentially or in combination, may be used to effectively treat mesangial proliferative glomerular disease.

Show MeSH
Related in: MedlinePlus