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牛磺酸可恢复血管平滑肌细胞钙化模型中的 Axl/Gas6 表达。

Taurine restores Axl/Gas6 expression in vascular smooth muscle cell calcification model.

机构信息

Department of Cardiothoracic Surgery, Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, 410011, Changsha, Hunan, China.

出版信息

Amino Acids. 2010 Jul;39(2):375-83. doi: 10.1007/s00726-009-0448-z. Epub 2009 Dec 24.

Abstract

Our previous studies demonstrated that taurine inhibits osteoblastic differentiation of vascular smooth muscular cells (VSMCs) via the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, but the underlying mechanism is not elucidated. The tyrosine kinase receptor Axl and its ligand growth arrest-specific protein 6 (Gas6) are expressed in VSMCs. Axl/Gas6 signaling system is known to inhibit VSMCs calcification. We herein showed that taurine partially restored Axl and Gas6 expression in beta-glycerophosphate (beta-GP)-induced VSMC calcification model. Taurine also induced activation of ERK, but not other two MAPKs including c-jun N-terminal Kinase (JNK) and p38 in VSMCs. Either knockdown of the taurine transporter (TAUT) or treatment with the ERK-specific inhibitor PD98059 blocked the activation of ERK by taurine and abolished taurine-induced Axl/Gas6 expression and calcium deposition reduction in beta-GP-induced VSMC calcification model. These results demonstrate for the first time that taurine stimulates expression of Axl and Gas6 via TAUT/ERK signaling pathway in beta-GP-induced VSMC calcification model.

摘要

我们之前的研究表明,牛磺酸通过丝裂原活化蛋白激酶/细胞外信号调节激酶(MAPK/ERK)信号通路抑制血管平滑肌细胞(VSMCs)的成骨分化,但潜在机制尚不清楚。酪氨酸激酶受体 Axl 及其配体生长停滞特异性蛋白 6(Gas6)在 VSMCs 中表达。已知 Axl/Gas6 信号系统可抑制 VSMCs 钙化。我们在此表明,牛磺酸部分恢复了β-甘油磷酸(β-GP)诱导的 VSMC 钙化模型中 Axl 和 Gas6 的表达。牛磺酸还诱导 ERK 激活,但不激活包括 c-jun N 末端激酶(JNK)和 p38 在内的其他两种 MAPK。牛磺酸转运体(TAUT)的敲低或 ERK 特异性抑制剂 PD98059 的处理阻断了牛磺酸对 ERK 的激活,并消除了牛磺酸诱导的 Axl/Gas6 表达和钙沉积减少在β-GP 诱导的 VSMC 钙化模型中。这些结果首次表明,牛磺酸通过 TAUT/ERK 信号通路刺激β-GP 诱导的 VSMC 钙化模型中 Axl 和 Gas6 的表达。

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