Department of Dermatology, College of Medicine, Chung‑Ang University, Seoul 06973, Republic of Korea.
Taeyoung Co., Ltd., Seongnam, Gyeonggi 13467, Republic of Korea.
Int J Mol Med. 2018 May;41(5):3090-3098. doi: 10.3892/ijmm.2018.3483. Epub 2018 Feb 12.
It has been established that glycosaminoglycans (GAGs) serve an important role in protecting the skin against the effects of aging. A previous clinical trial by our group identified that a cream containing GAGs reduced wrinkles and increased skin elasticity, dermal density and skin tightening. However, the exact molecular mechanism underlying the anti‑aging effect of GAGs has not yet been fully elucidated. The present study assessed the influence of GAGs on cell viability, collagen synthesis and collagen synthesis‑associated signaling pathways in tumor necrosis factor‑α (TNF‑α)‑stimulated human dermal fibroblasts (HDFs); an in vitro model of aging. The results demonstrated that GAGs restored type I collagen synthesis and secretion by inhibiting extracellular signal‑regulated kinase (ERK) signaling in TNF‑α‑stimulated HDFs. However, GAGs did not activate c‑jun N‑terminal kinase or p38. It was determined that GAGs suppressed the phosphorylation of downstream transcription factors of ERK activation, activator protein‑1 (AP‑1; c‑fos and c‑jun), leading to a decrease in matrix metalloproteinase‑1 (MMP‑1) levels and the upregulation of tissue inhibitor of metalloproteinase‑1 in TNF‑α‑stimulated HDFs. In addition, GAGs attenuated the apoptosis of HDFs induced by TNF‑α. The current study revealed a novel mechanism: GAGs serve a crucial role in ameliorating TNF‑α‑induced MMP‑1 expression, which causes type I collagen degeneration via the inactivation of ERK/AP‑1 signaling in HDFs. The results of the present study indicate the potential application of GAGs as effective anti‑aging agents that induce wrinkle reduction.
已经证实，糖胺聚糖（GAGs）在保护皮肤免受衰老影响方面起着重要作用。我们小组之前的一项临床试验表明，含有 GAGs 的乳膏可减少皱纹，增加皮肤弹性、真皮密度和紧致度。然而，GAGs 抗老化作用的确切分子机制尚未完全阐明。本研究评估了 GAGs 对肿瘤坏死因子-α（TNF-α）刺激的人真皮成纤维细胞（HDF）中细胞活力、胶原蛋白合成和胶原蛋白合成相关信号通路的影响；这是一种衰老的体外模型。结果表明，GAGs 通过抑制 TNF-α 刺激的 HDF 中细胞外信号调节激酶（ERK）信号，恢复了 I 型胶原蛋白的合成和分泌。然而，GAGs 没有激活 c-Jun N-末端激酶或 p38。研究确定 GAGs 抑制 ERK 激活下游转录因子的磷酸化，从而降低激活蛋白-1（AP-1；c-fos 和 c-jun）的基质金属蛋白酶-1（MMP-1）水平，并上调 TNF-α 刺激的 HDF 中的组织金属蛋白酶抑制剂-1。此外，GAGs 可减轻 TNF-α诱导的 HDF 凋亡。本研究揭示了一种新的机制：GAGs 通过使 ERK/AP-1 信号失活，在 HDF 中发挥重要作用，可改善 TNF-α 诱导的 MMP-1 表达，从而导致 I 型胶原蛋白降解。本研究结果表明 GAGs 作为有效的抗皱剂具有潜在的应用前景。
