Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.
Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.
复制标题
维生素 D3 预处理调节脂多糖诱导的急性肾损伤期间肾脏炎症反应
DOI：
10.1038/srep18687
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发表时间：
2015-12-22
影响因子：
4.6
通讯作者：
Xu DX
中科院分区：
文献类型：
--
作者：
Xu S;Chen YH;Tan ZX;Xie DD;Zhang C;Zhang ZH;Wang H;Zhao H;Yu DX;Xu DX
维生素D受体（VDR）在人类和小鼠肾脏中高度表达。然而，其功能仍然模糊不清。本研究探讨了维生素D3（VitD 3）预处理对脂多糖（LPS）诱导的急性肾损伤中肾脏炎症的影响。小鼠腹腔注射LPS。VitD 3 + LPS组于LPS注射前48、24、1h分别给予VitD 3（25 μg/kg）预处理。与预期的一样，在LPS处理的小鼠中观察到肾功能和病理损伤的明显降低。VitD 3预处理可明显减轻LPS引起的肾功能下降和病理损伤。此外，VitD 3预处理减弱LPS诱导的肾脏炎症细胞因子，趋化因子和粘附分子。此外，预处理与1，25（OH）2D 3，活性形式的维生素D3，减轻LPS诱导的上调炎症细胞因子和趋化因子在人HK-2细胞，肾小管上皮细胞系，在VDR依赖的方式。进一步分析表明，激活肾脏VDR的VitD 3特异性抑制LPS诱导的肾小管核因子κ B（NF-κB）p65亚单位的核转位。LPS可激活肾组织NF-κB，抑制肾组织VDR及其靶基因表达。此外，VitD 3还可增强VDR与NF-κB p65亚基之间的物理相互作用。这些结果提供了一个机制解释维生素D3介导的抗炎活性在LPS诱导的急性肾损伤。
Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury.