Age-related elevation of HGF is driven by the reduction of fibroblast size in a YAP/TAZ/CCN2 axis-dependent manner.
Age-related elevation of HGF is driven by the reduction of fibroblast size in a YAP/TAZ/CCN2 axis-dependent manner.
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DOI：
10.1016/j.jdermsci.2021.02.003
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发表时间：
2021-04
影响因子：
4.6
通讯作者：
Quan T
中科院分区：
文献类型：
--
作者：
Xiang Y;Qin Z;Yang Y;Fisher GJ;Quan T
人类皮肤老化主要是由于胶原蛋白的流失。肝细胞生长因子 (HGF) 通过抑制胶原蛋白的产生而发挥抗纤维化因子的作用。在老化的人类皮肤中，真皮成纤维细胞中的 HGF 升高，从而通过抑制胶原蛋白的产生而导致真皮老化（真皮薄）。我们的目的是研究年龄相关的 HGF 表达升高的潜在机制。老化皮肤真皮中的胶原纤维破碎且杂乱，这损害了胶原蛋白与成纤维细胞的相互作用，导致成纤维细胞的扩散和尺寸减少。为了探索真皮成纤维细胞大小减少与年龄相关的 HGF 表达升高之间的联系，我们操纵真皮成纤维细胞大小，并通过激光捕获显微切割、免疫染色、毛细管电泳免疫分析和定量 RT-PCR 研究 HGF 的细胞大小依赖性调节。我们发现成纤维细胞大小的减小是与年龄相关的 HGF 表达升高的原因。进一步的研究表明，细胞大小依赖性的 HGF 表达上调是由受阻的 YAP/TAZ 核易位及其靶基因 CCN2 介导的。相反，真皮成纤维细胞大小的恢复以 YAP/TAZ 依赖性方式迅速逆转了 HGF 的细胞大小依赖性上调。最后，我们证实在体内衰老人皮肤中，HGF表达升高伴随着YAP/TAZ和CCN2表达降低。与年龄相关的 HGF 升高是由成纤维细胞大小以 YAP/TAZ/CCN2 轴依赖性方式减少所驱动的。这些数据揭示了一种新的机制，通过这种机制，成纤维细胞大小的减少会上调 HGF 的表达，从而导致胶原蛋白的流失，而胶原蛋白是衰老人类皮肤的一个显着特征。
Aged human skin is primarily attributable to the loss of collagen. Hepatocyte growth factor (HGF) acts as an anti-fibrotic factor by suppression of collagen production. In aged human skin, HGF is elevated in dermal fibroblasts and thus contributes to dermal aging (thin dermis) by suppression of collagen production. We aimed to investigate the underlying mechanisms of age-related elevation of HGF expression. Collagen fibrils in the aged skin dermis are fragmented and disorganized, which impairs collagen-fibroblast interaction, resulting in reduced fibroblast spreading and size. To explore the connection between reduced dermal fibroblast size and age-related elevation of HGF expression, we manipulate dermal fibroblast size, and cell-size dependent regulation of HGF was investigated by laser capture microdissection, immunostaining, capillary electrophoresis immunoassay, and quantitative RT-PCR. We found that reduced fibroblast size is responsible for age-related elevation of HGF expression. Further investigation indicated that cell size-dependent upregulation of HGF expression was mediated by impeded YAP/TAZ nuclear translocation and their target gene, CCN2. Conversely, restoration of dermal fibroblast size rapidly reversed cell-size-dependent upregulation of HGF in a YAP/TAZ-dependent manner. Finally, we confirmed that elevated HGF expression is accompanied by the reduced expression of YAP/TAZ and CCN2 in the aged human skin in vivo. Age-related elevation of HGF is driven by the reduction of fibroblast size in a YAP/TAZ/CCN2 axis-dependent manner. These data reveal a novel mechanism by which reduction of fibroblast size upregulates HGF expression, which in turn contributes to loss of collagen, a prominent feature of aged human skin.
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DOI：
10.1186/s12964-018-0232-3
发表时间：
2018-04-25
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Qin Z;Xia W;Fisher GJ;Voorhees JJ;Quan T
通讯作者：
Quan T
影响因子：
11.2
作者：
Cheng, Nikki;Chytil, Anna;Mosesi, Harold L.
通讯作者：
Mosesi, Harold L.
影响因子：
7.5
作者：
Jacob, MP
通讯作者：
Jacob, MP
影响因子：
15.9
作者：
Fisher, GJ;Datta, S;Voorhees, JJ
通讯作者：
Voorhees, JJ
影响因子：
7.8
作者：
Qin Z;Voorhees JJ;Fisher GJ;Quan T
通讯作者：
Quan T