Department of Dermatology, St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Exp Dermatol. 2010 Aug;19(8):e258-64. doi: 10.1111/j.1600-0625.2010.01070.x.
Vitamin C is used as an anti-ageing agent because of its collagen enhancing effects. The precise cellular signalling mechanism of vitamin C is not well known. Here, we investigate the profibrotic mechanism of vitamin C against LL-37. Antimicrobial peptide LL-37 decreases collagen expression at mRNA and protein levels in human dermal fibroblasts (HDFs). The ability of LL-37 to inhibit collagen expression is dependent on phosphorylation of extracellular signal-regulated kinase (ERK). HDFs and human keloid fibroblasts were treated with vitamin C followed by 2 h of LL-37 treatment. Collagen mRNA expression and total soluble collagen production inhibited by LL-37 was enhanced by treatment with 0.5 mm vitamin C. Vitamin C also decreased intracellular reactive oxygen intermediates (ROI) levels that were increased by LL-37. Furthermore, the phosphorylation of ERK was analysed by Western blot following treatment with vitamin C and LL-37. Vitamin C turned off phosphorylation of ERK that was induced by LL-37. Ets-1 transcriptional factor, which is involved in the regulation of collagen expression by LL-37, was also inhibited by vitamin C. This study shows that vitamin C enhances collagen production by inhibiting the ERK pathway induced by LL-37.
维生素 C 因其增强胶原蛋白的作用而被用作抗衰老剂。维生素 C 的精确细胞信号机制尚不清楚。在这里，我们研究了维生素 C 对 LL-37 的抗纤维化机制。抗菌肽 LL-37 降低人真皮成纤维细胞 (HDF) 中 mRNA 和蛋白水平的胶原蛋白表达。LL-37 抑制胶原蛋白表达的能力依赖于细胞外信号调节激酶 (ERK) 的磷酸化。用维生素 C 处理 HDF 和人瘢痕成纤维细胞，然后用 LL-37 处理 2 小时。LL-37 抑制的胶原 mRNA 表达和总可溶性胶原产生被 0.5mm 维生素 C 处理增强。维生素 C 还降低了由 LL-37 增加的细胞内活性氧中间体 (ROI) 水平。此外，用维生素 C 和 LL-37 处理后通过 Western blot 分析 ERK 的磷酸化。维生素 C 关闭了由 LL-37 诱导的 ERK 的磷酸化。Ets-1 转录因子参与了 LL-37 对胶原蛋白表达的调节，也被维生素 C 抑制。这项研究表明，维生素 C 通过抑制 LL-37 诱导的 ERK 通路增强胶原蛋白的产生。
