title: Effect of immunosuppression on the human mesangial cell cycle.
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.
authors.affiliation: Department of Nephrology, Provincial People's Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Biruh
authors.initials: B
authors.lastname: Workeneh
authors.affiliation: Department of Nephrology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Nephrology, Provincial People's Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Rongshan
authors.initials: R
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects*; D009173:Mycophenolic Acid / Q000494:pharmacology; D011241:Prednisone / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus