Limits...
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.

Show MeSH

Related in: MedlinePlus

Tac prevents progression of the cell cycle of HMCs from G0/G1 to S phase. (A) Quiescent HMCs were treated with 10% fetal calf serum in the absence or presence of Tac (1 and 5 μmol/l) and their proliferation was assessed via MTT assay at 24, 48 and 72 h (*P<0.05 vs. 0 μmol/l). (B–D) Cell cycle progression of HMCs in response to various concentrations of Tac was analyzed by flow cytometry 48 h following treatment. (E) Statistical analysis indicated that upon exposure to 1 and 5 μmol/l Tac for 48 h, the percentage of HMCs in the S phase and G0/G1 phase was significantly altered (*P<0.01 vs. 0 μmol/l). (F) HMCs were treated with Tac (1 and 5 μmol/l) for 48 h and the apoptotic rate was assessed by flow cytometry. All values are presented as the mean ± standard deviation values of three independent experiments. Tac, tacrolimus; HMC, human mesangial cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4262500&req=5

f1-mmr-11-02-0910: Tac prevents progression of the cell cycle of HMCs from G0/G1 to S phase. (A) Quiescent HMCs were treated with 10% fetal calf serum in the absence or presence of Tac (1 and 5 μmol/l) and their proliferation was assessed via MTT assay at 24, 48 and 72 h (*P<0.05 vs. 0 μmol/l). (B–D) Cell cycle progression of HMCs in response to various concentrations of Tac was analyzed by flow cytometry 48 h following treatment. (E) Statistical analysis indicated that upon exposure to 1 and 5 μmol/l Tac for 48 h, the percentage of HMCs in the S phase and G0/G1 phase was significantly altered (*P<0.01 vs. 0 μmol/l). (F) HMCs were treated with Tac (1 and 5 μmol/l) for 48 h and the apoptotic rate was assessed by flow cytometry. All values are presented as the mean ± standard deviation values of three independent experiments. Tac, tacrolimus; HMC, human mesangial cell.

Mentions: The effects of Tac on the cell cycle of human mesangial cells were examined, firstly by treating human mesangial cells with Tac (1–5 μmol/l) and assessing their proliferation by an MTT assay. Cellular proliferation was significantly decreased following Tac treatment. This inhibitory effect occurred in a dose- and time-dependent manner (Fig. 1A). The effects of Tac on cell cycle progression were then examined (Fig. 1B–D). Upon exposure to 5 μmol/l Tac for 48 h, the percentage of cells in the S phase decreased by 41%, while the percentage of cells in G0/G1 phase increased by 30%. These results indicated that Tac prevented the progression of human mesangial cells into S phase (Fig. 1E). The effects of Tac on apoptosis of human mesangial cells were also examined. Tac (at 1 and 5 μmol/l) did not significantly alter the apoptotic rate of human mesangial cells following 48 h of treatment (Fig. 1F).


Effect of immunosuppression on the human mesangial cell cycle.

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

Tac prevents progression of the cell cycle of HMCs from G0/G1 to S phase. (A) Quiescent HMCs were treated with 10% fetal calf serum in the absence or presence of Tac (1 and 5 μmol/l) and their proliferation was assessed via MTT assay at 24, 48 and 72 h (*P<0.05 vs. 0 μmol/l). (B–D) Cell cycle progression of HMCs in response to various concentrations of Tac was analyzed by flow cytometry 48 h following treatment. (E) Statistical analysis indicated that upon exposure to 1 and 5 μmol/l Tac for 48 h, the percentage of HMCs in the S phase and G0/G1 phase was significantly altered (*P<0.01 vs. 0 μmol/l). (F) HMCs were treated with Tac (1 and 5 μmol/l) for 48 h and the apoptotic rate was assessed by flow cytometry. All values are presented as the mean ± standard deviation values of three independent experiments. Tac, tacrolimus; HMC, human mesangial cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-mmr-11-02-0910: Tac prevents progression of the cell cycle of HMCs from G0/G1 to S phase. (A) Quiescent HMCs were treated with 10% fetal calf serum in the absence or presence of Tac (1 and 5 μmol/l) and their proliferation was assessed via MTT assay at 24, 48 and 72 h (*P<0.05 vs. 0 μmol/l). (B–D) Cell cycle progression of HMCs in response to various concentrations of Tac was analyzed by flow cytometry 48 h following treatment. (E) Statistical analysis indicated that upon exposure to 1 and 5 μmol/l Tac for 48 h, the percentage of HMCs in the S phase and G0/G1 phase was significantly altered (*P<0.01 vs. 0 μmol/l). (F) HMCs were treated with Tac (1 and 5 μmol/l) for 48 h and the apoptotic rate was assessed by flow cytometry. All values are presented as the mean ± standard deviation values of three independent experiments. Tac, tacrolimus; HMC, human mesangial cell.
Mentions: The effects of Tac on the cell cycle of human mesangial cells were examined, firstly by treating human mesangial cells with Tac (1–5 μmol/l) and assessing their proliferation by an MTT assay. Cellular proliferation was significantly decreased following Tac treatment. This inhibitory effect occurred in a dose- and time-dependent manner (Fig. 1A). The effects of Tac on cell cycle progression were then examined (Fig. 1B–D). Upon exposure to 5 μmol/l Tac for 48 h, the percentage of cells in the S phase decreased by 41%, while the percentage of cells in G0/G1 phase increased by 30%. These results indicated that Tac prevented the progression of human mesangial cells into S phase (Fig. 1E). The effects of Tac on apoptosis of human mesangial cells were also examined. Tac (at 1 and 5 μmol/l) did not significantly alter the apoptotic rate of human mesangial cells following 48 h of treatment (Fig. 1F).

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