RESUMEN
Previous studies have found that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 or VD3] exerts many biological effects, including the inhibition of cell proliferation and induction of apoptosis, but its mechanism of action remains unclear. The goal of our investigation was to explore the effects of 1,25(OH)2D3 on the proliferation of cultured human mesangial cells and their expression of Ki67 in vitro, and to establish its mechanism of action. Cultured human mesangial cells were randomly divided into the following four groups: normal control (N group; administered Dulbecco's modified Eagle's medium containing 5% fetal bovine serum), proliferation [epidermal growth factor (EGF) group; administered 10 µg/L EGF], VD3 intervention [administered 10-8 M 1,25(OH)2D3], and proliferation and intervention [EGF+VD3 group; administered 10 µg/L EGF and 10-8 M 1,25(OH)2D3]. Cells were incubated for 48 h with the corresponding treatment, and fluorescence immunocytochemistry and reverse transcription-quantitative polymerase chain reaction were used to detect expression of Ki67 protein and mRNA, respectively. Compared to the N group, Ki67 levels were found to be higher in the EGF group but significantly lower in the VD3 intervention group. Moreover, expression of Ki67 by cells in the EGF+VD3 group was significantly lower than that of those in the EGF group. All of these differences were statistically significant (P < 0.05). In conclusion, 1,25(OH)2D3 inhibited Ki67 expression and the proliferation of human mesangial cells; therefore, Ki67 may be regarded as a potent therapeutic target in mesangial proliferative glomerulonephritis.
Asunto(s)
Proliferación Celular , Células Mesangiales/metabolismo , Vitamina D/análogos & derivados , Vitaminas/farmacología , Línea Celular , Factor de Crecimiento Epidérmico/genética , Factor de Crecimiento Epidérmico/metabolismo , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Células Mesangiales/efectos de los fármacos , Vitamina D/farmacologíaRESUMEN
To investigate the relationship of polymorphisms in the cholesteryl ester transport protein (CETP) gene with coronary heart disease (CHD) and diabetes in subjects of Uyghur and Han Chinese origin, 266 subjects with CHD including 154 subjects with type 2 diabetes mellitus and 136 healthy subjects (as a control group) were enrolled in this study. Polymerase chain reaction and an enzymatic assay based on the ligase detection reaction were used to detect R451Q polymorphisms in the CETP gene. The data were used for genotyping to determine the allele frequency distribution of the CETP gene R451Q polymorphism to investigate its effects on lipid and apolipoprotein levels. Genotype and allele frequencies of CETP R451QA did not show any significant differences among the CHD and healthy control groups. Moreover, no significant difference in the CETP R451QA genotype and allele frequency was detected among the subjects of Uyghur and Han origin. Blood levels of lipids and apolipoproteins likewise lacked an association with CETP R451QA genotype frequencies in the CHD/diabetes group. We conclude that the R451Q polymorphisms in the CETP gene had no effects on blood lipid levels and are not a risk factor for CHD in Han and Uyghur Chinese.