Apelin attenuates the osteoblastic differentiation of vascular smooth muscle cells.
Apelin attenuates the osteoblastic differentiation of vascular smooth muscle cells.
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apelin减轻了血管平滑肌细胞的成骨细胞分化。
DOI：
10.1371/journal.pone.0017938
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发表时间：
2011-03-18
期刊：
影响因子：
3.7
通讯作者：
Liao EY
中科院分区：
文献类型：
--
作者：
Shan PF;Lu Y;Cui RR;Jiang Y;Yuan LQ;Liao EY
血管钙化是血管平滑肌细胞（VSMCs）向成骨细胞分化的结果，是心血管疾病发病率和死亡率的主要危险因素。Apelin是最近发现的肽，其是孤儿G蛋白偶联受体APJ的内源性配体。几项研究已经确定了apelin对心血管系统的保护作用。然而，apelin对VSMCs成骨分化的影响和机制尚未阐明。以体外培养的钙化血管平滑肌细胞（CVMSCs）为模型，探讨apelin与VSMCs成骨分化的关系及其信号通路。检测CVSMCs碱性磷酸酶（ALP）活性和骨钙素分泌。使用细胞外信号调节激酶（ERK）抑制剂PD 98059、磷脂酰肌醇3-激酶（PI 3-K）抑制剂LY 294002和APJ siRNA研究了所涉及的信号通路。结果表明，apelin抑制ALP活性、骨钙素分泌和矿化结节的形成。在CVSMC中检测到APJ蛋白，并且apelin激活ERK和AKT（PI 3-K的下游效应物）。用siRNA抑制APJ可消除apelin诱导的ERK和Akt活化。此外，抑制APJ表达，以及ERK或PI 3-K的激活，逆转了apelin对ALP活性的影响。上述结果表明，apelin通过APJ/ERK和APJ/PI 3-K/AKT信号通路抑制CVSMCs向成骨细胞分化。Apelin似乎对动脉钙化起保护作用。
Vascular calcification, which results from a process osteoblastic differentiation of vascular smooth muscle cells (VSMCs), is a major risk factor for cardiovascular morbidity and mortality. Apelin is a recently discovered peptide that is the endogenous ligand for the orphan G-protein-coupled receptor, APJ. Several studies have identified the protective effects of apelin on the cardiovascular system. However, the effects and mechanisms of apelin on the osteoblastic differentiation of VSMCs have not been elucidated. Using a culture of calcifying vascular smooth muscle cells (CVMSCs) as a model for the study of vascular calcification, the relationship between apelin and the osteoblastic differentiation of VSMCs and the signal pathway involved were investigated. Alkaline phosphatase (ALP) activity and osteocalcin secretion were examined in CVSMCs. The involved signal pathway was studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002, and APJ siRNA. The results showed that apelin inhibited ALP activity, osteocalcin secretion, and the formation of mineralized nodules. APJ protein was detected in CVSMCs, and apelin activated ERK and AKT (a downstream effector of PI3-K). Suppression of APJ with siRNA abolished the apelin-induced activation of ERK and Akt. Furthermore, inhibition of APJ expression, and the activation of ERK or PI3-K, reversed the effects of apelin on ALP activity. These results showed that apelin inhibited the osteoblastic differentiation of CVSMCs through the APJ/ERK and APJ/PI3-K/AKT signaling pathway. Apelin appears to play a protective role against arterial calcification.
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影响因子：
4
作者：
Bing, Hai-Tao;Wang, Chen-Guang;Wang, Kui
通讯作者：
Wang, Kui
影响因子：
6
作者：
Hashimoto, Tatsuo;Kihara, Minoru;Umemura, Satoshi
通讯作者：
Umemura, Satoshi
影响因子：
4
作者：
Bear, Mackenzie;Butcher, Martin;Shaughnessy, Stephen G.
通讯作者：
Shaughnessy, Stephen G.
DOI：
10.1016/s0167-4889(00)00143-9
发表时间：
2001-04-23
影响因子：
5.1
作者：
Kawamata, Y;Fukusumi, S;Fujino, M
通讯作者：
Fujino, M
影响因子：
6.2
作者：
Kume, S;Kato, S;Nagata, K
通讯作者：
Nagata, K