Sonic hedgehog is a potent chemoattractant for human monocytes: diabetes mellitus inhibits Sonic hedgehog-induced monocyte chemotaxis.
Sonic hedgehog is a potent chemoattractant for human monocytes: diabetes mellitus inhibits Sonic hedgehog-induced monocyte chemotaxis.
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DOI：
10.1007/s00395-009-0047-x
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发表时间：
2010-01
影响因子：
9.5
通讯作者：
Waltenberger J
中科院分区：
文献类型：
--
作者：
Dunaeva M;Voo S;van Oosterhoud C;Waltenberger J
本研究的目的是评估对照（CTR）和患有或不患有冠状动脉疾病（CAD）的糖尿病患者的单核细胞中刺猬（Hh）信号分子的表达和声波刺猬（Shh）的趋化活性。此前的多项研究表明，外源性给予Shh可以诱导血管生成，加速缺血心肌和骨骼肌的修复。血样采集自 (1) CTR (n = 25)； (2) 没有糖尿病的稳定 CAD 患者（CAD−DM，n = 10）； (3) 具有稳定的 CAD 和 DM（CAD+DM，n = 15）。通过 Percoll 梯度分离单核细胞并进行 PCR 和趋化性分析。 Hh信号分子在人单核细胞中表达，并诱导单核细胞趋化。 Shh 刺激的单核细胞从 CTR 的迁移测量为 172.5 ± 90%，并且在 1 μg/ml 的 Shh 浓度下观察到最大刺激。然而，Shh 未能诱导单核细胞从 CAD+DM 迁移（94.3 ± 27%，与 CTR 相比，P < 0.001）。对Shh 的反应受损与受体Ptc 的强烈转录上调有关，而下游分子的表达没有改变。此外，Ptc 在人主动脉粥样硬化斑块的巨噬细胞中强烈表达。因此，Shh 是单核细胞的有效化学引诱剂，它激活与迁移相关的经典信号通路。 Shh 信号传导受到 DM 的负面影响，可能参与 DM 相关并发症的发病机制。
The aim of the present study was to evaluate the expression of hedgehog (Hh) signaling molecules and the chemotactic activity of Sonic hedgehog (Shh) in monocytes from control (CTR) and diabetic patients with or without coronary artery disease (CAD). Previously several studies demonstrated that exogenous administration of Shh can induce angiogenesis and accelerate repair of ischemic myocardium and skeletal muscles. Blood samples were collected from (1) CTR (n = 25); (2) patients with stable CAD without diabetes mellitus (CAD−DM, n = 10); and (3) with stable CAD with DM (CAD+DM, n = 15). Monocytes were isolated by Percoll gradient and subjected to PCR and chemotaxis analysis. Hh signaling molecules were expressed in human monocytes, and Shh-induced monocyte chemotaxis. Shh-stimulated migration of monocytes from CTR measured 172.5 ± 90% and a maximal stimulation was observed at Shh concentration of 1 μg/ml. However, Shh failed to induce migration of monocytes from CAD+DM (94.3 ± 27%, P < 0.001 vs. CTR). The impaired response to Shh was associated with strong transcriptional upregulation of the receptor Ptc, while expression of downstream molecules was not altered. Moreover, Ptc is strongly expressed in macrophages of human aortic atherosclerotic plaque. Thus, Shh is a potent chemoattractant for monocytes and it activates classical signaling pathways related to migration. The Shh signaling was negatively affected by DM which might be involved in the pathogenesis of DM-related complications.
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影响因子：
2
作者：
Cohen, MM
通讯作者：
Cohen, MM
影响因子：
4.6
作者：
Bouma, G;Coppens, JMC;Versnel, MA
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Versnel, MA
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Lutgens, E.
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Asai, Jun;Takenaka, Hideya;Losordo, Douglas W.
通讯作者：
Losordo, Douglas W.