1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines.
1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines.
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1,25(OH)2D3 缺乏通过分泌衰老相关炎症细胞因子诱导结肠炎症
DOI：
10.1371/journal.pone.0146426
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yuan X
中科院分区：
文献类型：
--
作者：
Liu Y;Chen L;Zhi C;Shen M;Sun W;Miao D;Yuan X
流行病学研究表明，1，25-二羟基维生素D[1，25（OH）2D 3]不足似乎与衰老和结肠癌有关，而潜在的生物学机制在很大程度上仍然未知。炎症性肠病是结肠癌的危险因素之一。在这项研究中，我们研究了1，25（OH）2D 3缺乏是否对25-羟基维生素D 1α-羟化酶敲除[Cyp 27 b1 −/−]小鼠的结肠有影响，这些小鼠从断奶到10个月龄喂养救援饮食（高钙、磷酸盐和乳糖）。我们发现1，25（OH）2D 3缺陷小鼠表现出显著的结肠炎症表型，包括结肠长度缩短、粘膜结构变薄和紊乱以及炎性细胞浸润。DNA损伤、细胞衰老和衰老相关炎性细胞因子的产生在Cyp 27 b1 −/−小鼠的结肠中也显著增加。此外，结肠中ROS的水平显著增加，而Cyp 27 b1 −/−小鼠结肠中抗氧化基因的表达水平显著下调。综上所述，我们的研究结果表明，1，25（OH）2D 3缺乏可诱导结肠炎症，这可能是由于氧化应激和DNA损伤增加，随后诱导细胞衰老和衰老相关分泌因子的过量产生。因此，我们的研究结果表明，1，25（OH）2D 3可能在预防结肠炎症和结肠癌的发展和进展中发挥重要作用。
Epidemiological studies showed that 1,25-Dihydroxyvitamin D[1,25(OH)2D3] insufficiency appears to be associated with aging and colon cancer while underlying biological mechanisms remain largely unknown. Inflammatory bowel disease is one of the risk factors for colon cancer. In this study, we investigated whether 1,25(OH)2D3 deficiency has an impact on the colon of 25-hydroxyvitamin D 1α-hydroxylase knockout [Cyp27b1−/−] mice fed on a rescue diet (high calcium, phosphate, and lactose) from weaning to 10 months of age. We found that 1,25(OH)2D3 deficient mice displayed significant colon inflammation phenotypes including shortened colon length, thinned and disordered mucosal structure, and inflammatory cell infiltration. DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were also increased significantly in the colon of Cyp27b1−/−mice. Furthermore, the levels of ROS in the colon were increased significantly, whereas the expression levels of antioxidative genes were down-regulated dramatically in the colon of Cyp27b1−/−mice. Taken together, our results demonstrated that 1,25(OH)2D3 deficiency could induce colon inflammation, which may result from increased oxidative stress and DNA damage, subsequently, induced cell senescence and overproduction of senescence-associated secretory factors. Therefore, our findings suggest that 1,25(OH)2D3 may play an important role in preventing the development and progression of colon inflammation and colon cancer.