Liver X receptor-activating ligands modulate renal and intestinal sodium-phosphate transporters.
Liver X receptor-activating ligands modulate renal and intestinal sodium-phosphate transporters.
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DOI：
10.1038/ki.2011.159
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发表时间：
2011-09
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
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胆固醇通过atp结合盒转运体被泵出不同组织的细胞，包括脉管系统、肠、肝和肾。激活肝脏X受体（LXR）的配体调节这种外排。在这里，我们确定了LXR激动剂对磷酸盐转运蛋白调控的作用。磷酸盐稳态是由肠道和肾脏磷酸钠（NaPi）转运体的协同作用调节的，这种调节的缺失导致高磷血症。用DMHCA或TO901317（两种LXR激动剂，可预防ApoE或LDLR敲除小鼠动脉粥样硬化）治疗的小鼠，显著降低了肠道和肾脏近端管刷边界膜钠梯度依赖性磷酸盐摄取的活性，降低了血清磷酸盐，增加了尿磷酸盐排泄。DMHCA的作用是由于肠道和肾脏NaPi转运蛋白丰度的显著降低。同样的效果也被发现在负鼠肾细胞培养后，用任何激动剂治疗。内源性LXR受体的核表达增加，NaPi4蛋白丰度（负鼠细胞中主要的II型NaPi转运蛋白）降低，NaPi共转运活性降低。因此，LXR激动剂调节肠道和肾脏NaPi转运蛋白，进而调节血清磷酸盐水平。
Cholesterol is pumped out of the cells in different tissues, including the vasculature, intestine, liver, and kidney, by the ATP-binding cassette transporters. Ligands that activate the liver X receptor (LXR) modulate this efflux. Here we determined the effects of LXR agonists on the regulation of phosphate transporters. Phosphate homeostasis is regulated by the coordinated action of the intestinal and renal sodium–phosphate (NaPi) transporters, and the loss of this regulation causes hyperphosphatemia. Mice treated with DMHCA or TO901317, two LXR agonists that prevent atherosclerosis in ApoE or LDLR knockout mice, significantly decreased the activity of intestinal and kidney proximal tubular brush border membrane sodium gradient-dependent phosphate uptake, decreased serum phosphate, and increased urine phosphate excretion. The effects of DMHCA were due to a significant decrease in the abundance of the intestinal and renal NaPi transport proteins. The same effect was also found in opossum kidney cells in culture after treatment with either agonist. There was increased nuclear expression of the endogenous LXR receptor, a reduction in NaPi4 protein abundance (the main type II NaPi transporter in the opossum cells), and a reduction in NaPi co-transport activity. Thus, LXR agonists modulate intestinal and renal NaPi transporters and, in turn, serum phosphate levels.
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影响因子：
20.1
作者：
Miyazaki-Anzai S;Levi M;Kratzer A;Ting TC;Lewis LB;Miyazaki M
通讯作者：
Miyazaki M
DOI：
10.1038/labinvest.2008.114
发表时间：
2009-01
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.182412699
发表时间：
2002-09-03
影响因子：
11.1
作者：
Hernando, N;Déliot, N;Murer, H
通讯作者：
Murer, H
影响因子：
6.5
作者：
Quinet, EM;Savio, DA;Nambi, P
通讯作者：
Nambi, P
DOI：
10.1073/pnas.112059299
发表时间：
2002-05-28
影响因子：
11.1
作者：
Joseph, SB;McKilligin, E;Tontonoz, P
通讯作者：
Tontonoz, P