AIM: To investigate the possible involvement of 25-hydroxyvitamin D3-1α-hydroxylase [1α-25(OH)2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells.METHODS: Caco-2 cells were incubated ...AIM: To investigate the possible involvement of 25-hydroxyvitamin D3-1α-hydroxylase [1α-25(OH)2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells.METHODS: Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 μmol/L 25(OH)2D3 or with 1μmol/L 1α-25(OH)2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25(OH)2D3 or 1α-25(OH)2D3.1α-25(OH)2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25(OH)2D3 protein.Finally, enzymatic activity was measured by ELISA.RESULTS: Both butyrate and 1α-25(OH)2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25(OH)2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25(OH)2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites.CONCLUSION: Our experimental data pr ovide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25(OH)2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25(OH)2D3 in combination with butyrate may offer a new therapeutic approach for the treatment of colon cancer.展开更多
维生素D抵抗是一类罕见的遗传性疾病,由于维生素D活化过程障碍或维生素D受体(VDR)功能异常所致,其发病与基因突变有关,1α-羟化酶基因突变所致的称为HVDRR-Ⅰ型,维生素D受体基因突变所致的称为H V D R R-Ⅱ型,两型的临床表现相类似,均...维生素D抵抗是一类罕见的遗传性疾病,由于维生素D活化过程障碍或维生素D受体(VDR)功能异常所致,其发病与基因突变有关,1α-羟化酶基因突变所致的称为HVDRR-Ⅰ型,维生素D受体基因突变所致的称为H V D R R-Ⅱ型,两型的临床表现相类似,均有严重的低血钙、继发性甲状旁腺激素功能亢进以及早发的严重佝偻病等。HVDRR-Ⅰ型对活性维生素D治疗反应较好,HVDRR-Ⅱ型需较大剂量骨化三醇治疗,同时补充钙剂,可改善某些患者的临床症状及影像学结果。如果活性维生素D治疗效果欠佳,可考虑给予大剂量钙剂治疗。展开更多
肺癌是发病率和死亡率均较高的肿瘤之一,现有的预防和治疗方法均收效甚微。维生素D的生物学特性除了通过促进机体钙的吸收进而调节多种生理功能外,其在肿瘤的预防和治疗方面也有一定的作用。肺癌的发生、发展与维生素D或其代谢物25-一...肺癌是发病率和死亡率均较高的肿瘤之一,现有的预防和治疗方法均收效甚微。维生素D的生物学特性除了通过促进机体钙的吸收进而调节多种生理功能外,其在肿瘤的预防和治疗方面也有一定的作用。肺癌的发生、发展与维生素D或其代谢物25-一羟维生素D[25(OH)D]或1,25-二羟维生素D[1,25(OH)2D]有密切的关系。在这一代谢通路中,25-羟维生素D 1-α-羟化酶和25-羟基维生素D3-24-羟化酶的活性决定了1,25(OH)2D的含量,而维生素D受体(vitamin D receptor,VDR)的表达决定了1,25(OH)2D是否能有效发挥作用。本文就维生素D与肺癌的发生和预后之间的关系以及维生素D的代谢通路做一综述。展开更多
基金Supported by the Else Kroner-Fresenius Foundation, Bad Homburg, Germany
文摘AIM: To investigate the possible involvement of 25-hydroxyvitamin D3-1α-hydroxylase [1α-25(OH)2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells.METHODS: Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 μmol/L 25(OH)2D3 or with 1μmol/L 1α-25(OH)2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25(OH)2D3 or 1α-25(OH)2D3.1α-25(OH)2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25(OH)2D3 protein.Finally, enzymatic activity was measured by ELISA.RESULTS: Both butyrate and 1α-25(OH)2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25(OH)2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25(OH)2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites.CONCLUSION: Our experimental data pr ovide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25(OH)2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25(OH)2D3 in combination with butyrate may offer a new therapeutic approach for the treatment of colon cancer.
文摘维生素D抵抗是一类罕见的遗传性疾病,由于维生素D活化过程障碍或维生素D受体(VDR)功能异常所致,其发病与基因突变有关,1α-羟化酶基因突变所致的称为HVDRR-Ⅰ型,维生素D受体基因突变所致的称为H V D R R-Ⅱ型,两型的临床表现相类似,均有严重的低血钙、继发性甲状旁腺激素功能亢进以及早发的严重佝偻病等。HVDRR-Ⅰ型对活性维生素D治疗反应较好,HVDRR-Ⅱ型需较大剂量骨化三醇治疗,同时补充钙剂,可改善某些患者的临床症状及影像学结果。如果活性维生素D治疗效果欠佳,可考虑给予大剂量钙剂治疗。
文摘肺癌是发病率和死亡率均较高的肿瘤之一,现有的预防和治疗方法均收效甚微。维生素D的生物学特性除了通过促进机体钙的吸收进而调节多种生理功能外,其在肿瘤的预防和治疗方面也有一定的作用。肺癌的发生、发展与维生素D或其代谢物25-一羟维生素D[25(OH)D]或1,25-二羟维生素D[1,25(OH)2D]有密切的关系。在这一代谢通路中,25-羟维生素D 1-α-羟化酶和25-羟基维生素D3-24-羟化酶的活性决定了1,25(OH)2D的含量,而维生素D受体(vitamin D receptor,VDR)的表达决定了1,25(OH)2D是否能有效发挥作用。本文就维生素D与肺癌的发生和预后之间的关系以及维生素D的代谢通路做一综述。
