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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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Related in: MedlinePlus

MP prevents HMCs from entering S phase. (A) Quiescent HMCs were treated with 10% fetal calf serum in the absence and presence of MP (1 and 10 mg/l) and subjected to an MTT assay (*P<0.05 vs. 0 mg/l). (B–D) At 48 h, the cell cycle progression was assessed by flow cytometry. (E) Statistical analysis of B–D (*P<0.05 vs. 0 μmol/l). (F) Statistical analysis of the apoptotic rate assessed by flow cytometry. At 10 mg/l for 48 h, MP significantly increased apoptosis in HMCs (*P<0.01 vs. 0 μmol/l). Values are expressed as the mean ± standard deviation of six independent experiments. MP, methylprednisolone; HMC, human mesangial cell.
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f3-mmr-11-02-0910: MP prevents HMCs from entering S phase. (A) Quiescent HMCs were treated with 10% fetal calf serum in the absence and presence of MP (1 and 10 mg/l) and subjected to an MTT assay (*P<0.05 vs. 0 mg/l). (B–D) At 48 h, the cell cycle progression was assessed by flow cytometry. (E) Statistical analysis of B–D (*P<0.05 vs. 0 μmol/l). (F) Statistical analysis of the apoptotic rate assessed by flow cytometry. At 10 mg/l for 48 h, MP significantly increased apoptosis in HMCs (*P<0.01 vs. 0 μmol/l). Values are expressed as the mean ± standard deviation of six independent experiments. MP, methylprednisolone; HMC, human mesangial cell.

Mentions: The influence of MP on human mesangial cell growth has not previously been studied, to the best of our knowledge. At concentrations of 1 and 10 mg/l, MP inhibited the proliferation of human mesangial cells in a dose- and time-dependent manner (Fig. 3A). It was also determined that at concentrations of 1 and 10 mg/l, MP significantly decreased the percentage of cells in S phase, while increasing the percentage of cells in G0/G1 phase (Fig. 3B–E). Similarly to CsA, MP (1–10 mg/l) significantly increased the apoptotic rate in human mesangial cells following 48 h of treatment (Fig. 3F).


Effect of immunosuppression on the human mesangial cell cycle.

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

MP prevents HMCs from entering S phase. (A) Quiescent HMCs were treated with 10% fetal calf serum in the absence and presence of MP (1 and 10 mg/l) and subjected to an MTT assay (*P<0.05 vs. 0 mg/l). (B–D) At 48 h, the cell cycle progression was assessed by flow cytometry. (E) Statistical analysis of B–D (*P<0.05 vs. 0 μmol/l). (F) Statistical analysis of the apoptotic rate assessed by flow cytometry. At 10 mg/l for 48 h, MP significantly increased apoptosis in HMCs (*P<0.01 vs. 0 μmol/l). Values are expressed as the mean ± standard deviation of six independent experiments. MP, methylprednisolone; HMC, human mesangial cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-mmr-11-02-0910: MP prevents HMCs from entering S phase. (A) Quiescent HMCs were treated with 10% fetal calf serum in the absence and presence of MP (1 and 10 mg/l) and subjected to an MTT assay (*P<0.05 vs. 0 mg/l). (B–D) At 48 h, the cell cycle progression was assessed by flow cytometry. (E) Statistical analysis of B–D (*P<0.05 vs. 0 μmol/l). (F) Statistical analysis of the apoptotic rate assessed by flow cytometry. At 10 mg/l for 48 h, MP significantly increased apoptosis in HMCs (*P<0.01 vs. 0 μmol/l). Values are expressed as the mean ± standard deviation of six independent experiments. MP, methylprednisolone; HMC, human mesangial cell.
Mentions: The influence of MP on human mesangial cell growth has not previously been studied, to the best of our knowledge. At concentrations of 1 and 10 mg/l, MP inhibited the proliferation of human mesangial cells in a dose- and time-dependent manner (Fig. 3A). It was also determined that at concentrations of 1 and 10 mg/l, MP significantly decreased the percentage of cells in S phase, while increasing the percentage of cells in G0/G1 phase (Fig. 3B–E). Similarly to CsA, MP (1–10 mg/l) significantly increased the apoptotic rate in human mesangial cells following 48 h of treatment (Fig. 3F).

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