Phosphate and pyrophosphate mediate PKA-induced vascular cell calcification.
Phosphate and pyrophosphate mediate PKA-induced vascular cell calcification.
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磷酸盐和焦磷酸盐介导PKA诱导的血管细胞钙化。
DOI：
10.1016/j.bbrc.2008.07.062
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发表时间：
2008-09-26
影响因子：
3.1
通讯作者：
Tintut, Yin
中科院分区：
文献类型：
--
作者：
Huang, Michael S.;Sage, Andrew P.;Lu, Jinxiu;Demer, Linda L.;Tintut, Yin
血管钙化与心血管风险增加相关，并通过血管细胞的骨软骨分化发生。许多控制骨骼矿化的相同调节因子，包括控制激活剂无机磷酸盐和有效抑制剂焦磷酸盐水平的复杂代谢途径，也控制血管钙化。我们以前发现cAMP/PKA信号通路介导了肿瘤坏死因子-α 1和氧化磷脂等炎症因子诱导的体外血管细胞钙化。在这份报告中，我们测试了这种信号通路是否调节磷酸盐和焦磷酸盐代谢。用PKA激活剂毛喉素处理原代鼠主动脉细胞可显著诱导成骨细胞分化标志物，包括碱性磷酸酶（ALP）、骨桥蛋白、骨钙素以及焦磷酸生成剂、外核苷酸-焦磷酸酶/磷酸二酯酶-1（Enpp 1）和焦磷酸转运蛋白、强直蛋白，但不诱导钠/磷酸协同转运蛋白Pit-1。在碱性磷酸酶，β-甘油磷酸，产生无机磷酸盐的底物的存在下，毛喉素也增强了基质矿化。ALP或Pit-1抑制剂可抑制毛喉素诱导的骨桥蛋白表达和矿化，但不能抑制毛喉素诱导的骨钙素或ALP。这些结果表明，磷酸是必不可少的PKA诱导的血管细胞钙化和PKA诱导的钙化的程度是由反馈诱导的抑制剂，焦磷酸盐控制。
Vascular calcification is associated with increased cardiovascular risk and occurs by osteochondrogenic differentiation of vascular cells. Many of the same regulatory factors that control skeletal mineralization, including the complex metabolic pathway controlling levels of the activator, inorganic phosphate, and the potent inhibitor, pyrophosphate, also govern vascular calcification. We previously found that cAMP/PKA signaling pathway mediates in vitro vascular cell calcification induced by inflammatory factors including tumor necrosis factor-alpha 1 and oxidized phospholipids. In this report, we tested whether this signaling pathway modulates phosphate and pyrophosphate metabolism. Treatment of primary murine aortic cells with the PKA activator, forskolin, significantly induced osteoblastic differentiation markers, including alkaline phosphatase (ALP), osteopontin, osteocalcin as well as the pyrophosphate generator, ectonucleotide-pyrophosphatase/phosphodiesterase-1 (Enpp1) and the pyrophosphate transporter, ankylosis protein, but not the sodium/phosphate cotransporter, Pit-1. In the presence of a substrate for ALP, beta-glycerophosphate, which generates inorganic phosphate, forskolin also enhanced matrix mineralization. Inhibitors of ALP or Pit-1 abrogated forskolin-induced osteopontin expression and mineralization but not forskolin-induced osteocalcin or ALP. These results suggest that phosphate is necessary for PKA-induced calcification of vascular cells and that the extent of PKA-induced calcification is controlled by feedback induction of the inhibitor, pyrophosphate.
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影响因子：
20.1
作者：
Li, XW;Yang, HY;Giachelli, CM
通讯作者：
Giachelli, CM
影响因子：
6.2
作者：
Johnson, K;Goding, J;Terkeltaub, R
通讯作者：
Terkeltaub, R
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19.6
作者：
Chen, N. X.;Duan, D.;Moe, S. M.
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Moe, S. M.
影响因子：
13.2
作者：
Giachelli, CM;Jono, S;Morii, H
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Morii, H
影响因子：
3.7
作者：
Beck, GR;Moran, E;Knecht, N
通讯作者：
Knecht, N