Acceleration of Collagen Breakdown by Extracellular Basic pH in Human Dermal Fibroblasts.

BACKGROUND/AIMS Wound healing is a complex regeneration process involving the degradation and reassembly of connective tissues and skin layers. Previous studies have shown that pH plays a significant role in both the direct and indirect regulation of cellular processes in the wound, which, in turn, affect the wound healing process. However, the effects of pH on the collagen breakdown component of wound healing have yet to be investigated. Therefore, we investigated the induction of accelerated collagen breakdown by pH imbalance in the skin. METHODS Na+/H+ exchanger and metalloproteinase (MMP)-1 were analyzed spectrophotometrically, and the expression of collagen type-I-alpha-1 (COL1A1) and mitogen-activated protein kinase (MAPK) was measured by Western blotting. RESULTS Accelerated collagen breakdown induced by extracellular basic pH via the overproduction of reactive oxygen species (ROS) and MAPK signaling was examined in skin fibroblasts and in a three-dimensional human skin equivalent system. Basic pH (>7.50) upregulated MMP-1 and downregulated COL1A1 levels via ROS generation and MAPK signaling pathways. Acidic pH (<6.04) slightly upregulated MMP-1 and slightly downregulated COL1A1 levels via ROS generation and the p38 signaling pathway. CONCLUSION Our results indicate that skin pH is an important effector of collagen formation in wound healing. This finding will aid in the development of new pH-targeted therapeutic strategies.