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Article

Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells

  • Authors:
    • Liping Zou
    • Wenjuan Wang
    • Zude Xu
    • Nong Zhang
    • Tao Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
  • Pages: 409-416
    |
    Published online on: May 14, 2012
       https://doi.org/10.3892/ijmm.2012.997
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Abstract

Aldose reductase (AR), the first and the rate-limiting enzyme of the polyol pathway, has been implicated in platelet-derived growth factor (PDGF)-induced proliferation of rat mesangial cells (MsCs). It is well known that AR plays an important role in various chronic diabetic complications, for example, diabetic nephropathy. Moreover, our previous studies have demonstrated that an AR inhibitor (ARI) significantly reduced the proliferation of rat MsCs induced by PDGF, however, the mechanism remains unclear. The aim of the present study was to elucidate the molecular mechanisms through which AR regulates PDGF-induced rat MsC proliferation. It was demonstrated that PDGF-induced MsC proliferation was significantly inhibited by pretreatment with ARI. Cell cycle analysis by flow cytometry revealed that ARI prevented the entry of cells from the G1 into the S phase. Furthermore, the effect of the PI3K/Akt signaling pathway on the cell cycle was analyzed. The PI3K/Akt pathway was activated with PDGF treatment. However, ARI blocked Akt activation in response to PDGF. Moreover, PDGF increased the levels of p21Cip1 cyclin kinase inhibitor protein in MsC, which was markedly inhibited by pretreatment with ARI. Conversely, PDGF significantly reduced the levels of the p27Kip1 cyclin kinase inhibitor protein, which was also restored by pretreatment with ARI. In conclusion, AR is involved in PDGF-induced rat MsC proliferation, and may serve as a potential target for the inhibition of MsC proliferation in several types of glomerulonephritis.
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Copy and paste a formatted citation
Spandidos Publications style
Zou L, Wang W, Xu Z, Zhang N and Jiang T: Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells. Int J Mol Med 30: 409-416, 2012.
APA
Zou, L., Wang, W., Xu, Z., Zhang, N., & Jiang, T. (2012). Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells. International Journal of Molecular Medicine, 30, 409-416. https://doi.org/10.3892/ijmm.2012.997
MLA
Zou, L., Wang, W., Xu, Z., Zhang, N., Jiang, T."Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells". International Journal of Molecular Medicine 30.2 (2012): 409-416.
Chicago
Zou, L., Wang, W., Xu, Z., Zhang, N., Jiang, T."Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells". International Journal of Molecular Medicine 30, no. 2 (2012): 409-416. https://doi.org/10.3892/ijmm.2012.997
Copy and paste a formatted citation
x
Spandidos Publications style
Zou L, Wang W, Xu Z, Zhang N and Jiang T: Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells. Int J Mol Med 30: 409-416, 2012.
APA
Zou, L., Wang, W., Xu, Z., Zhang, N., & Jiang, T. (2012). Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells. International Journal of Molecular Medicine, 30, 409-416. https://doi.org/10.3892/ijmm.2012.997
MLA
Zou, L., Wang, W., Xu, Z., Zhang, N., Jiang, T."Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells". International Journal of Molecular Medicine 30.2 (2012): 409-416.
Chicago
Zou, L., Wang, W., Xu, Z., Zhang, N., Jiang, T."Aldose reductase regulates platelet-derived growth factor-induced proliferation through mediating cell cycle progression in rat mesangial cells". International Journal of Molecular Medicine 30, no. 2 (2012): 409-416. https://doi.org/10.3892/ijmm.2012.997
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