Syndecan-1 regulates vascular smooth muscle cell phenotype.
Syndecan-1 regulates vascular smooth muscle cell phenotype.
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DOI：
10.1371/journal.pone.0089824
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Baker AB
中科院分区：
文献类型：
--
作者：
Chaterji S;Lam CH;Ho DS;Proske DC;Baker AB
我们研究了syndecan-1在调节血管平滑肌细胞表型的内源性炎症因子和改变疾病或损伤诱导的血管重塑中发生的微环境中的作用。血管平滑肌细胞（vSMC）表现出一系列在血管重塑过程中可以改变的表型。虽然多配体蛋白聚糖已成为细胞功能的强大而复杂的调节剂，但它们在控制vSMC表型中的作用尚不清楚。在这里，我们从野生型（WT）和syndecan-1敲除（S1KO）小鼠中分离vSMC。基因表达和蛋白质印迹研究表明，相对于WT细胞，S1KO中α-平滑肌肌动蛋白（α-SMA）、钙调蛋白和其他vSMC特异性分化标志物的水平降低。发现S1KO细胞的扩散面积大于WT细胞，粘着斑形成、Src磷酸化和肌动蛋白细胞骨架排列的改变相应增加。此外，S1KO导致S6RP磷酸化增加，AKT和PKC-α磷酸化减少。为了检查这些变化是否存在于体内，对来自老龄WT和S1KO小鼠的分离的胎盘进行钙调蛋白染色。与我们的体外研究结果一致，WT小鼠睾丸相对于S1KO的钙调蛋白染色更高。当暴露于炎性细胞因子TNF-α时，WT vSMC的syndecan-1表达降低了80%。此外，与WT相比，使用TNF-α时，S1 KO vSMC产生的促炎细胞因子增加。最后，使用抑制肽合成抑素抑制syndecan-1与整合素α v β 3和α v β 5之间的相互作用似乎对vSMC具有与敲除syndecan-1类似的作用，vSMC分化标志物的表达降低，炎性细胞因子、受体和骨桥蛋白的表达增加。总之，我们的结果支持syndecan-1促进vSMC分化和静止。因此，多配体蛋白聚糖-1的存在将对vSMC去分化具有保护作用，并且该活性与整合素α v β 3和α v β 5的相互作用有关。
We examined the role of syndecan-1 in modulating the phenotype of vascular smooth muscle cells in the context of endogenous inflammatory factors and altered microenvironments that occur in disease or injury-induced vascular remodeling. Vascular smooth muscle cells (vSMCs) display a continuum of phenotypes that can be altered during vascular remodeling. While the syndecans have emerged as powerful and complex regulators of cell function, their role in controlling vSMC phenotype is unknown. Here, we isolated vSMCs from wild type (WT) and syndecan-1 knockout (S1KO) mice. Gene expression and western blotting studies indicated decreased levels of α-smooth muscle actin (α-SMA), calponin, and other vSMC-specific differentiation markers in S1KO relative to WT cells. The spread area of the S1KO cells was found to be greater than WT cells, with a corresponding increase in focal adhesion formation, Src phosphorylation, and alterations in actin cytoskeletal arrangement. In addition, S1KO led to increased S6RP phosphorylation and decreased AKT and PKC-α phosphorylation. To examine whether these changes were present in vivo, isolated aortae from aged WT and S1KO mice were stained for calponin. Consistent with our in-vitro findings, the WT mice aortae stained higher for calponin relative to S1KO. When exposed to the inflammatory cytokine TNF-α, WT vSMCs had an 80% reduction in syndecan-1 expression. Further, with TNF-α, S1KO vSMCs produced increased pro-inflammatory cytokines relative to WT. Finally, inhibition of interactions between syndecan-1 and integrins αvβ3 and αvβ5 using the inhibitory peptide synstatin appeared to have similar effects on vSMCs as knocking out syndecan-1, with decreased expression of vSMC differentiation markers and increased expression of inflammatory cytokines, receptors, and osteopontin. Taken together, our results support that syndecan-1 promotes vSMC differentiation and quiescence. Thus, the presence of syndecan-1 would have a protective effect against vSMC dedifferentiation and this activity is linked to interactions with integrins αvβ3 and αvβ5.
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影响因子：
20.1
作者：
GALIS, ZS;MUSZYNSKI, M;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
5
作者：
Der, P;Cui, JH;Das, DK
通讯作者：
Das, DK
影响因子：
14
作者：
Das, Subhamoy;Singh, Gunjan;Baker, Aaron B.
通讯作者：
Baker, Aaron B.
DOI：
10.1084/jem.20081278
发表时间：
2009-03-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Beauvais DM;Ell BJ;McWhorter AR;Rapraeger AC
通讯作者：
Rapraeger AC
影响因子：
37.8
作者：
Borissoff, Julian Ilcheff;Heeneman, Sylvia;Spronk, Henri M. H.
通讯作者：
Spronk, Henri M. H.