Department of Cardiothoracic Surgery, Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, 410011, Changsha, Hunan, China.
Amino Acids. 2010 Jul;39(2):375-83. doi: 10.1007/s00726-009-0448-z. Epub 2009 Dec 24.
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.
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。
