Effect and mechanism of all-trans retinoic acid on cyclosporin-induced proliferation and apoptosis of glomerular mesangial cells
10.3969/j.issn.1674-7445.2017.06.011
- VernacularTitle:全反式维甲酸对环孢素诱导的肾小球系膜细胞增殖与凋亡的影响及其机制
- Author:
Xu CHEN
1
;
Jianhua WU
;
Naifeng GUO
;
Yaping FAN
;
Xiaolan CHEN
Author Information
1. 南通大学附属医院肾内科
- Keywords:
All-trans retinoic acid (ATRA);
Cyclosporin (CsA);
Mesangial cell,glomerulus;
Smac protein;
Rejection reaction;
Cell proliferation;
Apoptosis;
Renal toxicity
- From:
Organ Transplantation
2017;8(6):465-471
- CountryChina
- Language:Chinese
-
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.
