Bioscience Research Institute, AmorePacific Corporation R&D Center, Yongin, Republic of Korea.
J Dermatol Sci. 2012 Apr;66(1):51-9. doi: 10.1016/j.jdermsci.2011.12.008. Epub 2011 Dec 22.
Ultraviolet (UV) A irradiation causes the degeneration of extracellular matrix in the skin dermis, mainly due to disrupted collagen homeostasis, resulting in the photo-aging of human skin. All-trans retinoic acid (ATRA) improves photo-aged human skin in vivo.
Although the effects of ATRA on collagen synthesis and MMP regulation are well known, the effects of ATRA on other collagen homeostasis-associated genes have not been elucidated. This study was aimed to study the factors that are pharmacologically associated with the effect of ATRA on collagen homeostasis.
The gene transcription profile of collagen homeostasis-associated genes was systematically evaluated in three-dimensional human dermal equivalents (HDEs) following UVA-irradiation and/or ATRA treatment.
In addition to the expected changes in MMPs and collagen synthesis in HDEs in response to ATRA, prolidase, an important enzyme in the recycling of proline and hydroxyproline from degraded collagen molecules, was significantly decreased by UVA irradiation, and its down-regulation was antagonized by ATRA. Transfection with a prolidase-specific siRNA led to a significant decrease in procollagen synthesis in human fibroblasts. ATRA inhibited the UVA irradiation-induced decrease in prolidase activity through an insulin-like growth factor (IGF) receptor signaling pathway in HDEs. ARTA increased IGF1 and IGF2 production in HDEs, and neutralizing IGFs with anti-IGF antibodies abolished the effect of ATRA on proliase activity.
These data demonstrate that ATRA regulates prolidase activity in HDEs via IGF receptor signaling, suggesting one of the pharmacological mechanisms by which improves photo-aged human skin.
紫外线（UV）A 照射会导致皮肤真皮层细胞外基质的退化，主要是由于胶原稳态的破坏，导致人类皮肤的光老化。全反式维甲酸（ATRA）可改善体内光老化的人类皮肤。
尽管 ATRA 对胶原合成和 MMP 调节的作用众所周知，但 ATRA 对其他胶原稳态相关基因的作用尚未阐明。本研究旨在研究与 ATRA 对胶原稳态作用相关的药理学相关因素。
在三维人真皮等效物（HDE）中，系统评估 UVA 照射和/或 ATRA 处理后与胶原稳态相关的基因转录谱。
除了 ATRA 对 HDE 中 MMP 和胶原合成的预期变化外，脯氨酸酶（从降解的胶原分子中回收脯氨酸和羟脯氨酸的重要酶）在 UVA 照射下显著降低，其下调被 ATRA 拮抗。脯氨酸酶特异性 siRNA 的转染导致人成纤维细胞中前胶原合成显著减少。ATRA 通过 HDE 中的胰岛素样生长因子（IGF）受体信号通路抑制 UVA 照射诱导的脯氨酸酶活性降低。ATRA 增加 HDE 中的 IGF1 和 IGF2 产生，并用抗 IGF 抗体中和 IGF 可消除 ATRA 对脯氨酸酶活性的作用。
这些数据表明，ATRA 通过 IGF 受体信号通路调节 HDE 中的脯氨酸酶活性，提示改善光老化人类皮肤的药理学机制之一。
