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

Journal of Nephrology
Baofeng SuYaping Fan

Abstract

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

Citations

Jan 11, 2019·International Journal of Cancer. Journal International Du Cancer·Yehui DuPenghong Song
Jan 3, 2019·American Journal of Physiology. Endocrinology and Metabolism·Masanori TamakiToshio Doi
Jul 16, 2013·Cellular and Molecular Neurobiology·Zhe ShiKe Wang
Jul 29, 2018·The Journal of Pharmacology and Experimental Therapeutics·Steven E TrasinoLorraine J Gudas
Nov 25, 2018·Journal of Clinical Medicine·Yi-Chun TsaiYa-Ling Hsu

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