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J Nephrol. 2012 Nov-Dec;25(6):1031-40. doi: 10.5301/jn.5000090.

All-trans retinoic acid inhibits mesangial cell proliferation by up-regulating p21Waf1/Cip1 and p27Kip1 and down-regulating Skp2.

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  • 1Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, PR China.

Abstract

BACKGROUND:

The aim of this study was to examine effects of all-trans retinoic acid (ATRA) on rat mesangial cell proliferation, apoptosis and underlying mechanisms.

METHODS:

Cultured HBZY-1 rat mesangial cells received the following treatments: group 1: controls (DMSO); group 2: TGF-beta(1) (10 µg/L); groups 3-5: ATRA (0.1, 1.0 and 10 µmol/L) + TGF-beta(1) (10 µg/L). After treatments, the cells were studied by CCK-8 assay, cell cycle assay and TUNEL staining. p21(Waf1/Cip1), p27(Kip1) and Skp2 mRNA levels were measured by real-time PCR. p21(Waf1/Cip1), p27(Kip1) and Skp2 protein levels were detected by Western blot. The localization of p21(Waf1/Cip1) and p27(Kip1) proteins was observed by immunofluorescence and confocal microscopy.

RESULTS:

Compared with controls, TGF-beta(1) significantly enhanced proliferation and inhibited apoptosis of mesangial cells. ATRA dose-dependently reversed both TGF-beta(1)-induced decreases in p21(Waf1/Cip1) mRNA and protein levels and p27(Kip1) protein level and increases in Skp2 mRNA and protein levels, and inhibited TGF-beta(1)-induced proliferation through G(1) arrest. Meanwhile, after ATRA treatments, p21(Waf1/Cip1) and p27(Kip1) proteins mainly localized in the nucleus, and their concentrations in cytoplasm decreased.

CONCLUSION:

ATRA inhibited TGF-beta(1)-induced mesangial cell proliferation by up-regulating p21(Waf1/Cip1) mRNA and protein levels, and p27(Kip1) protein level, and down-regulating Skp2 mRNA and protein levels, but it had no significant effect on apoptosis in rat mesangial cells.

PMID:
22344541
[PubMed - indexed for MEDLINE]
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