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.
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.
Authors: Chu-Fang Chou; Yu-Hua Hsieh; Clinton J Grubbs; Venkatram R Atigadda; James A Mobley; Reinhard Dummer; Donald D Muccio; Isao Eto; Craig A Elmets; W Timothy Garvey; Pi-Ling Chang Journal: J Dermatol Sci Date: 2018-03-15 Impact factor: 4.563
Authors: Steven E Trasino; Xiao-Han Tang; Maria M Shevchuk; Mary E Choi; Lorraine J Gudas Journal: J Pharmacol Exp Ther Date: 2018-07-27 Impact factor: 4.030
Authors: Que Thanh Thanh Nguyen; Thi Xoan Hoang; Hyunjin Ryu; Kook-Hwan Oh; Jae Young Kim Journal: Biomed Res Int Date: 2021-10-06 Impact factor: 3.411