Endothelial cells downregulate apolipoprotein D expression in mural cells through paracrine secretion and Notch signaling.
Endothelial cells downregulate apolipoprotein D expression in mural cells through paracrine secretion and Notch signaling.
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内皮细胞通过旁分泌和 Notch 信号传导下调壁细胞中载脂蛋白 D 的表达。
DOI：
10.1152/ajpheart.00116.2011
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Lilly,Brenda
中科院分区：
文献类型：
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作者：
Pajaniappan,Mohanasundari;Glober,NancyK;Kennard,Simone;Liu,Hua;Zhao,Ning;Lilly,Brenda
内皮细胞和壁细胞的相互作用对于血管的正常形成和功能至关重要。这两种类型的细胞沟通，以调节血管功能的多个方面。在研究这种相互作用所调控的基因时，我们确定了载脂蛋白D（APOD）作为一个在与内皮细胞共培养的壁细胞中下调的基因。APOD是一种分泌型糖蛋白，与应激反应、脂质代谢和衰老有关。此外，已知APOD调节平滑肌细胞，并且在动脉粥样硬化病变中大量存在。我们的数据表明，在壁细胞的APOD的调节是双峰。内皮细胞旁分泌导致APOD表达部分下调。此外，细胞接触依赖性Notch信号传导也起作用。壁细胞上的NOTCH 3可能通过与内皮细胞上的JAGGED-1配体相互作用促进APOD的下调。我们的研究结果表明，NOTCH3有助于APOD的下调，本身就足以减弱APOD转录本的表达。在研究的后果，降低APOD表达的壁细胞，我们表明，APOD负调节细胞粘附。APOD通过减少焦点接触来减弱粘附;然而，它对应力纤维形成没有影响。这些数据揭示了一种新的机制，其中内皮细胞通过下调APOD来控制邻近的壁细胞，APOD反过来又通过调节粘附来影响壁细胞功能。
Endothelial and mural cell interactions are vitally important for proper formation and function of blood vessels. These two cell types communicate to regulate multiple aspects of vessel function. In studying genes regulated by this interaction, we identified apolipoprotein D (APOD) as one gene that is downregulated in mural cells by coculture with endothelial cells. APOD is a secreted glycoprotein that has been implicated in governing stress response, lipid metabolism, and aging. Moreover, APOD is known to regulate smooth muscle cells and is found in abundance within atherosclerotic lesions. Our data show that the regulation of APOD in mural cells is bimodal. Paracrine secretion by endothelial cells causes partial downregulation of APOD expression. Additionally, cell contact-dependent Notch signaling plays a role. NOTCH3 on mural cells promotes the downregulation of APOD, possibly through interaction with the JAGGED-1 ligand on endothelial cells. Our results show that NOTCH3 contributes to the downregulation of APOD and by itself is sufficient to attenuate APOD transcript expression. In examining the consequence of decreased APOD expression in mural cells, we show that APOD negatively regulates cell adhesion. APOD attenuates adhesion by reducing focal contacts; however, it has no effect on stress fiber formation. These data reveal a novel mechanism in which endothelial cells control neighboring mural cells through the downregulation of APOD, which, in turn, influences mural cell function by modulating adhesion.