Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation.
Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation.
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DOI：
10.1038/ki.2008.453
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发表时间：
2008-11
影响因子：
19.6
通讯作者：
Hewison, Martin
中科院分区：
文献类型：
--
作者：
Zehnder, Daniel;Quinkler, Marcus;Eardley, Kevin S.;Bland, Rosemary;Lepenies, Julia;Hughes, Susan V.;Raymond, Neil T.;Howie, Alexander J.;Cockwell, Paul;Stewart, Paul M.;Hewison, Martin
为了研究1，25-二羟基维生素D（1，25（OH）2D）在慢性肾脏疾病相关炎症中的任何潜在作用，我们测量了174例患有各种肾脏疾病的患者的维生素D代谢物，炎症标志物和基因表达。尿MCP-1蛋白和肾巨噬细胞浸润均与血清1，25（OH）2D水平显著负相关。以尿MCP-1作为二元结果的Logistic回归分析显示，血清1，25（OH）2D或25 OHD增加10个单位可导致较低的肾脏炎症。对111例肾活检的分析发现，肾损伤与维生素D激活酶25-羟基维生素D-1α-羟化酶（CYP 27 B1）、其分解代谢对应物24-羟化酶或维生素D受体的mRNA代偿性增加无关。然而，组织MCP-1和CYP 27 B1之间存在显著相关性。与慢性缺血性疾病患者相比，急性肾脏炎症患者的尿液和组织MCP-1、巨噬细胞浸润、巨噬细胞和肾上皮细胞CYP 27 B1表达显著增加，但血清1，25（OH）2D水平显著降低，尽管肾损伤水平相似。在体外，1，25（OH）2D减弱TNFα诱导的人近端小管细胞MCP-1表达。我们的研究表明，肾脏炎症与血清维生素D代谢物减少有关，并涉及旁分泌/自分泌维生素D系统的激活。
To examine any potential role for 1,25-dihydroxyvitamin D (1,25(OH)2D) in inflammation associated with chronic kidney disease we measured vitamin D metabolites, markers of inflammation and gene expression in 174 patients with a variety of kidney diseases. Urinary MCP-1 protein and renal macrophage infiltration were each significantly but inversely correlated with serum 1,25(OH)2D levels. Logistic regression analysis with urinary MCP-1 as binary outcome showed that a 10-unit increase in serum 1,25(OH)2D or 25OHD resulted in lower renal inflammation. Analysis of 111 renal biopsies found that renal injury was not associated with a compensatory increase in mRNA for the vitamin D-activating enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1), its catabolic counterpart 24-hydroxylase, or the vitamin D receptor. There was, however, a significant association between tissue MCP-1 and CYP27B1. Patients with acute renal inflammation had a significant increase in urinary and tissue MCP-1, macrophage infiltration, and macrophage and renal epithelial CYP27B1 expression but significantly lower levels of serum 1,25(OH)2D in comparison to patients with chronic ischemic disease despite similar levels of renal damage. In vitro, 1,25(OH)2D attenuated TNFα-induced MCP-1 expression by human proximal tubule cells. Our study indicates that renal inflammation is associated with decreased serum vitamin D metabolites and involves activation of the paracrine/autocrine vitamin D system.
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DOI：
10.1016/j.jsbmb.2004.03.089
发表时间：
2004-05-01
影响因子：
4.1
作者：
Anderson, PH;O'Loughlin, PD;Morris, HA
通讯作者：
Morris, HA
影响因子：
4.8
作者：
St-Arnaud, R;Arabian, A;Glorieux, FH
通讯作者：
Glorieux, FH
影响因子：
4.3
作者：
Adorini, L
通讯作者：
Adorini, L
影响因子：
4.8
作者：
Ren, SY;Nguyen, L;Hewison, M
通讯作者：
Hewison, M
影响因子：
15.9
作者：
Li, YC;Kong, J;Cao, LP
通讯作者：
Cao, LP