Kim Kang-Hoon, Jung Ji Hoon, Chung Won-Seok, Lee Chang-Hun, Jang Hyeung-Jin
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
Biomedicines. 2021 Apr 22;9(5):459. doi: 10.3390/biomedicines9050459.
Injured tissue triggers complex interactions through biological process associated with keratins. Rapid recovery is most important for protection against secondary infection and inflammatory pain. For rapid wound healing with minimal pain and side effects, shilajit has been used as an ayurvedic medicine. However, the mechanisms of rapid wound closure are unknown. Here, we found that shilajit induced wound closure in an acute wound model and induced migration in skin explant cultures through evaluation of transcriptomics via microarray testing. In addition, ferulic acid (FA), as a bioactive compound, induced migration via modulation of keratin 6α (K6α) and inhibition of β-catenin in primary keratinocytes of skin explant culture and injured full-thickness skin, because accumulation of β-catenin into the nucleus acts as a negative regulator and disturbs migration in human epidermal keratinocytes. Furthermore, FA alleviated wound-induced inflammation via activation of nuclear factor erythroid-2-related factor 2 (Nrf2) at the wound edge. These findings show that FA is a novel therapeutic agent for wound healing that acts via inhibition of β-catenin in keratinocytes and by activation of Nrf2 in wound-induced inflammation.
受损组织通过与角蛋白相关的生物学过程引发复杂的相互作用。快速恢复对于预防继发性感染和炎性疼痛最为重要。为了实现快速伤口愈合且疼痛和副作用最小，希拉季特已被用作一种阿育吠陀药物。然而，快速伤口闭合的机制尚不清楚。在此，我们发现希拉季特在急性伤口模型中诱导伤口闭合，并通过微阵列测试评估转录组学，在皮肤外植体培养物中诱导迁移。此外，阿魏酸（FA）作为一种生物活性化合物，通过调节角蛋白6α（K6α）和抑制皮肤外植体培养物和全层受损皮肤的原代角质形成细胞中的β-连环蛋白来诱导迁移，因为β-连环蛋白在细胞核中的积累作为一种负调节因子，会干扰人表皮角质形成细胞的迁移。此外，FA通过激活伤口边缘的核因子红细胞2相关因子2（Nrf2）减轻伤口诱导的炎症。这些发现表明，FA是一种用于伤口愈合的新型治疗剂，其作用机制是抑制角质形成细胞中的β-连环蛋白，并在伤口诱导的炎症中激活Nrf2。
