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Article Open Access

Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle

  • Authors:
    • Yanfang Gao
    • Hui Yang
    • Yanhong Wang
    • Jihua Tian
    • Rongshan Li
    • Xiaoshuang Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, The Affiliated People's Hospital of Shanxi Medical University, Shanxi Provincial People's Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi 030001, P.R. China, Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
    Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1582-1592
    |
    Published online on: August 7, 2020
       https://doi.org/10.3892/ijmm.2020.4696
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Abstract

The inhibition of mesangial cell proliferation has become an important therapy for the prevention of glomerular proliferation‑associated diseases. The combined application of immunosuppressants with multiple targets presents a novel direction in the treatment of kidney diseases. The present study was designed to explore the inhibitory effects of tacrolimus (TAC) combined with mycophenolate mofetil (MMF) on the proliferation of mesangial cells based on the cell cycle. In vitro, the levels of the proliferation index markers, Ki67 and cyclin D1, in human mesangial cells (HMCs) were determined by immunofluorescence staining and western blot analysis, respectively. In mice with lupus nephritis (LN), the proliferation of mesangial cells was determined using PAS and Masson's trichrome staining, while immunohistochemistry was used to detect Ki67 and western blot analysis was employed for the evaluation of cyclin D1 levels. The expression of platelet‑derived growth factor (PDGF), a proliferation‑associated protein, was estimated using immunohistochemistry and western blot analysis. In patients with LN, Ki67, cyclin D1 and PDGF expression was estimated by immunohistochemistry. The transforming growth factor‑β1/Smad pathway influenced by TAC and the p38 pathway influenced by MMF were also examined by western blot analysis. The results suggested that the combination of TAC and MMF at half the concentration based on the cell cycle was more effective than monotherapy in inhibiting mesangial cell proliferation in vitro and in vivo. TAC inhibited HMC proliferation by affecting the Smad2 signaling pathway. MMF inhibited HMC proliferation by affecting the p38 signaling pathway. Combined treatment with TAC and MMF significantly improved the clinical indexes of patients with LN without severe adverse effects. On the whole, the findings of the present study validate and reinforce the potential use of the combination of TAC and MMF for the treatment of mesangial proliferative diseases.
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Spandidos Publications style
Gao Y, Yang H, Wang Y, Tian J, Li R and Zhou X: Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle. Int J Mol Med 46: 1582-1592, 2020.
APA
Gao, Y., Yang, H., Wang, Y., Tian, J., Li, R., & Zhou, X. (2020). Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle. International Journal of Molecular Medicine, 46, 1582-1592. https://doi.org/10.3892/ijmm.2020.4696
MLA
Gao, Y., Yang, H., Wang, Y., Tian, J., Li, R., Zhou, X."Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle". International Journal of Molecular Medicine 46.4 (2020): 1582-1592.
Chicago
Gao, Y., Yang, H., Wang, Y., Tian, J., Li, R., Zhou, X."Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle". International Journal of Molecular Medicine 46, no. 4 (2020): 1582-1592. https://doi.org/10.3892/ijmm.2020.4696
Copy and paste a formatted citation
x
Spandidos Publications style
Gao Y, Yang H, Wang Y, Tian J, Li R and Zhou X: Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle. Int J Mol Med 46: 1582-1592, 2020.
APA
Gao, Y., Yang, H., Wang, Y., Tian, J., Li, R., & Zhou, X. (2020). Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle. International Journal of Molecular Medicine, 46, 1582-1592. https://doi.org/10.3892/ijmm.2020.4696
MLA
Gao, Y., Yang, H., Wang, Y., Tian, J., Li, R., Zhou, X."Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle". International Journal of Molecular Medicine 46.4 (2020): 1582-1592.
Chicago
Gao, Y., Yang, H., Wang, Y., Tian, J., Li, R., Zhou, X."Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle". International Journal of Molecular Medicine 46, no. 4 (2020): 1582-1592. https://doi.org/10.3892/ijmm.2020.4696
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