The nuclear hormone receptor peroxisome proliferator-activated receptor β/δ potentiates cell chemotactism, polarization, and migration
The nuclear hormone receptor peroxisome proliferator-activated receptor β/δ potentiates cell chemotactism, polarization, and migration
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DOI：
10.1128/mcb.00436-07
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发表时间：
2007-10-01
影响因子：
5.3
通讯作者：
Michalik, Liliane
中科院分区：
文献类型：
--
作者：
Tan, Nguan Soon;Icre, Guillaume;Michalik, Liliane
损伤后，角化细胞获得创面再上皮化所必需的可塑性。在这里，我们确定了一种新的途径，通过这种途径，核激素受体，直到现在更好地了解其代谢功能，增强细胞迁移。我们发现过氧化物酶体增殖物激活受体β / δ (PPAR β / δ)增强了两种磷脂酰肌醇3-激酶依赖的途径，即Akt和Rho-GTPase途径。这种PPAR β / δ活性增强了角质形成细胞对趋化信号的反应，促进了整合素的循环和肌动蛋白细胞骨架的重塑，从而促进了细胞迁移。通过三维伤口重建，我们证明这些缺陷对体内皮肤愈合有很强的影响，因为PPAR β / δ(-/-)小鼠表现出意想不到的罕见上皮化表型。我们的研究结果表明，核激素受体不仅在生物体水平上调节细胞间通讯，而且还参与细胞对趋化信号的反应。考虑到这里描述的机制在许多生理和病理情况下都很重要，我们的发现可能具有深远的意义。
After an injury, keratinocytes acquire the plasticity necessary for the reepithelialization of the wound. Here, we identify a novel pathway by which a nuclear hormone receptor, until now better known for its metabolic functions, potentiates cell migration. We show that peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) enhances two phosphatidylinositol 3-kinase-dependent pathways, namely, the Akt and the Rho-GTPase pathways. This PPAR beta/delta activity amplifies the response of keratinocytes to a chemotactic signal, promotes integrin recycling and remodeling of the actin cytoskeleton, and thereby favors cell migration. Using three-dimensional wound reconstructions, we demonstrate that these defects have a strong impact on in vivo skin healing, since PPAR beta/delta(-/-) mice show an unexpected and rare epithelialization phenotype. Our findings demonstrate that nuclear hormone receptors not only regulate intercellular communication at the organism level but also participate in cell responses to a chemotactic signal. The implications of our findings may be far-reaching, considering that the mechanisms described here are important in many physiological and pathological situations.