GALNT3, a gene associated with hyperphosphatemic familial tumoral calcinosis, is transcriptionally regulated by extracellular phosphate and modulates matrix metalloproteinase activity.
GALNT3, a gene associated with hyperphosphatemic familial tumoral calcinosis, is transcriptionally regulated by extracellular phosphate and modulates matrix metalloproteinase activity.
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DOI：
10.1016/j.bbadis.2008.09.016
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发表时间：
2009-01
影响因子：
6.2
通讯作者：
Sprecher, Eli
中科院分区：
文献类型：
--
作者：
Chefetz, Ilana;Kohno, Kimitoshi;Izumi, Hiroto;Uitto, Jouni;Richard, Gabriele;Sprecher, Eli
GALNT3编码udp - n -乙酰- α - d -半乳糖胺：多肽n -乙酰半乳糖氨基转移酶3 (ppGalNacT3)，一种糖基转移酶，已被认为可以阻止FGF23的蛋白水解，FGF23是一种有效的磷酸化蛋白。因此，GALNT3的功能缺失突变导致高磷血症家族性肿瘤钙化症（HFTC），这是一种罕见的常染色体隐性遗传病，表现为肾脏对磷酸盐的重吸收增加，导致严重的高磷血症和广泛的异位钙化。虽然这些发现明确地归因于ppGalNacT3在调节磷酸盐稳态中的作用，但目前对调节GALNT3表达的因素知之甚少。此外，GALNT3在外周组织中表达降低的影响目前还没有研究。在目前的研究中，我们证明GALNT3的表达受到许多已知与磷酸盐稳态相关的因素的调控，包括无机磷酸盐本身、钙和1,25-二羟基维生素D3。此外，我们发现GALNT3在人皮肤成纤维细胞中的表达降低会导致FGF7和基质金属蛋白酶的表达增加，这在之前被认为与异位钙化的发病机制有关。因此，目前的数据表明ppGalNacT3可能在外周组织中发挥作用，可能与磷酸盐代谢障碍的发病机制相关。
GALNT3 encodes UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl-transferarase 3 (ppGalNacT3), a glycosyltransferase which has been suggested to prevent proteolysis of FGF23, a potent phosphaturic protein. Accordingly, loss-of-function mutations in GALNT3 cause hyperphosphatemic familial tumoral calcinosis (HFTC), a rare autosomal recessive disorder manifesting with increased kidney reabsorption of phosphate, resulting in severe hyperphosphatemia and widespread ectopic calcifications. Although these findings definitely attribute a role to ppGalNacT3 in the regulation of phosphate homeostasis, little is currently known about the factors regulating GALNT3 expression. In addition, the effect of decreased GALNT3 expression in peripheral tissues has not been explored so far. In the present study, we demonstrate that GALNT3 expression is under the regulation of a number of factors known to be associated with phosphate homeostasis, including inorganic phosphate itself, calcium and 1,25-dihydroxyvitamin D3. In addition, we show that decreased GALNT3 expression in human skin fibroblasts leads to increased expression of FGF7 and of matrix metalloproteinases, which have been previously implicated in the pathogenesis of ectopic calcification. Thus, the present data suggest that ppGalNacT3 may play a role in peripheral tissues of potential relevance to the pathogenesis of disorders of phosphate metabolism.
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影响因子：
3.5
作者：
Barbieri, Anna Maria;Filopanti, Marcello;Beck-Peccoz, Paolo
通讯作者：
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作者：
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