Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels
Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels
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DOI：
10.1046/j.1523-1755.2003.00820.x
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发表时间：
2003-03-01
影响因子：
19.6
通讯作者：
Chen, NX
中科院分区：
文献类型：
--
作者：
Moe, SM;Duan, D;Chen, NX
背景骨基质蛋白在透析患者钙化的动脉中表达，表明血管平滑肌细胞（VSMCs）可能转化为成骨细胞样细胞。成骨细胞分化的关键转录调节因子之一是Cbfa 1。因此，我们假设这可能是动脉钙化的关键因素。为了验证这一假设，我们检查了尿毒症患者的腹壁下动脉的存在Cbfa 1和I型胶原和骨桥蛋白的原位杂交和免疫染色的部分。我们还通过逆转录-聚合酶链反应（RT-PCR）检测了来自透析患者的合并尿毒症血清对体外培养的牛VSMCs中Cbfa 1表达的影响。cbfa 1和骨桥蛋白在钙化血管的中膜和内膜中都有表达，但在非钙化血管中只有极轻微的染色。体外研究表明，与对照血清相比，尿毒症血清可诱导牛VSMCs表达Cbfa 1，其诱导机制为时间依赖性、非磷介导。这些结果支持Cbfa 1是透析患者中观察到的血管钙化的关键调节因子，并且在对许多尿毒症毒素的反应中上调。
Background. Bone matrix proteins are expressed in calcified arteries from dialysis patients, suggesting that vascular smooth muscle cells (VSMCs) may transform to osteoblast-like cells. One of the key transcriptional regulators of osteoblast differentiation is Cbfa1. Thus, we hypothesized that this may be a key factor in arterial calcification.Methods. To test this hypothesis, we examined sections of the inferior epigastric artery from uremic patients for the presence of Cbfa1 and type I collagen and osteopontin by in situ hybridization and immunostaining. We also examined the effect of pooled uremic sera from dialysis patients on the expression of Cbfa1 by reverse transcription-polymerase chain reaction (RT-PCR) in bovine VSMCs in vitro.Results. Cbfa1 and osteopontin were expressed in both the media and the intima in vessels that were calcified, but there was only minimal staining in non-calcified vessels. In vitro studies demonstrated that pooled uremic serum, compared to pooled control human serum induced the expression of Cbfa1 by RT-PCR in bovine VSMCs in a time-dependent, nonphosphorus-mediated mechanism.Conclusion. These results support that Cbfa1 is a key regulatory factor in the vascular calcification observed in dialysis patients and is up-regulated in response to many uremic toxins.