Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, Naju-si, Korea.
The Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea.
J Cell Mol Med. 2021 Apr;25(7):3646-3653. doi: 10.1111/jcmm.16472. Epub 2021 Mar 16.
Extracellular basic pH regulates cellular processes in wounds, and consequently influenced wound healing. Oxidative defence system modulation in the skin helps heal wounds, inhibits skin ageing and improves the skin condition. Moreover, the role of keratinocyte growth factor (KGF) and nuclear factor erythroid 2-related factor 2 (Nrf2) in antioxidant systems has been reported in various skin models. However, the effects of extracellular basic pH on wound- or skin ageing-related skin damage have not been examined. Thus, we investigated the antioxidant systems affected by extracellular basic pH in a 3D human skin equivalent system (3HSE). Extracellular basic pH decreased KGF expression and enhanced the oxidative defence system, and thus activated Nrf2 in the 3HSE. Additionally, extracellular basic pH and KGF treatment up-regulated Nrf2 activation and its regulation of the oxidative defence system in the 3HSE. This indicates that Nrf2 up-regulation is enhanced by reactive oxygen species production, rather than KGF, and by extracellular basic pH of the skin. The inhibition of skin damage through pH imbalance and KGF regulation suggests that the development of pH-regulating or pH-maintaining materials may provide effective therapeutic strategies for maintaining a healthy skin.
细胞外碱性 pH 值调节伤口中的细胞过程，从而影响伤口愈合。皮肤中氧化防御系统的调节有助于伤口愈合、抑制皮肤衰老和改善皮肤状况。此外，角蛋白细胞生长因子 (KGF) 和红细胞生成素相关因子 2 (Nrf2) 在各种皮肤模型中的抗氧化系统中的作用已被报道。然而，细胞外碱性 pH 值对与伤口或皮肤衰老相关的皮肤损伤的影响尚未被检查。因此，我们在 3D 人体皮肤等效物系统 (3HSE) 中研究了细胞外碱性 pH 值影响的抗氧化系统。细胞外碱性 pH 值降低了 KGF 的表达并增强了氧化防御系统，从而激活了 3HSE 中的 Nrf2。此外，细胞外碱性 pH 值和 KGF 处理上调了 Nrf2 的激活及其对 3HSE 中氧化防御系统的调节。这表明 Nrf2 的上调是由活性氧的产生增强的，而不是 KGF，并且是由皮肤的细胞外碱性 pH 值增强的。通过 pH 值失衡和 KGF 调节抑制皮肤损伤表明，开发 pH 值调节或维持材料可能为维持健康皮肤提供有效的治疗策略。
