Volume 8 Issue 6
Nov.  2017
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Article Navigation >  ORGAN TRANSPLANTATION  > 2017  >  8(6): 465-471
Chen Xu, Wu Jianhua, Guo Naifeng, et al. Effect and mechanism of all-trans retinoic acid on cyclosporin-induced proliferation and apoptosis of glomerular mesangial cells[J]. ORGAN TRANSPLANTATION, 2017, 8(6): 465-471. doi: 10.3969/j.issn.1674-7445.2017.06.011
Citation: Chen Xu, Wu Jianhua, Guo Naifeng, et al. Effect and mechanism of all-trans retinoic acid on cyclosporin-induced proliferation and apoptosis of glomerular mesangial cells[J]. ORGAN TRANSPLANTATION, 2017, 8(6): 465-471. doi: 10.3969/j.issn.1674-7445.2017.06.011
shu

Effect and mechanism of all-trans retinoic acid on cyclosporin-induced proliferation and apoptosis of glomerular mesangial cells

doi: 10.3969/j.issn.1674-7445.2017.06.011

  • Department of Nephrology, the Affiliated Hospital of Nantong University, Nantong 226001, China

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  • Corresponding author: Chen Xiaolan, Email: chenxl8448@sina.com
  • Received Date: 2017-08-30
    Available Online: 2021-01-19
  • Publish Date: 2017-11-15
    Abstract
  •   Objective  To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on the cyclosporin (CsA)-induced proliferation and apoptosis of glomerular mesangial cells in rat models.  Methods  The glomerular mesangial cells induced by different doses of CsA were treated with different doses of ATRA. MTT assay was carried out to detect cell proliferation. Hoechst 33258 fluorescent staining was adopted to observe the morphology of the apoptotic cells. Flow cytometry was conducted to detect the cellular apoptosis rate. Immunofluorescent staining was employed to quantitatively measure the expression level of mitochondria-derived pro-apoptotic Smac protein.  Results  Compared with the control group, administration of CsA at a dose of 0.5 μg/mL and above could suppress cellular proliferation, and use of CsA at a dose of 1.0 μg/mL and above could induce cellular apoptosis. The expression level of Smac protein was significantly up-regulated by CsA administration with a dose and time dependence (all P < 0.05).Compared with the CsA group, combined administration of CsA and ATRA exerted a more significant inhibitory effect on cellular proliferation. Supplement of ATRA could significantly inhibit glomerular mesangial cellular apoptosis induced by CsA and down-regulate the expression of Smac protein with a dose dependence (both P < 0.05).  Conclusions  CsA can inhibit cellular proliferation, induce cellular apoptosis and up-regulate the expression of Smac protein of glomerular mesangial cells. ATRA is capable of suppressing glomerular mesangial cellular apoptosis induced by CsA, which is probably mediated by the Smac signaling pathway.

     

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