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

Area of Science:

• Biochemistry
• Dermatology
• Wound Healing Research

Background:

• Wound healing involves complex tissue regeneration and is influenced by pH.
• The role of pH in collagen breakdown during wound healing remains under-investigated.

Purpose of the Study:

• To investigate how pH imbalance in skin affects collagen breakdown.
• To explore the molecular mechanisms underlying pH-induced collagen degradation.

Main Methods:

• Analysis of Na+/H+ exchanger and metalloproteinase (MMP)-1.
• Western blotting for collagen type-I-alpha-1 (COL1A1) and mitogen-activated protein kinase (MAPK) expression.
• Experiments conducted on skin fibroblasts and a 3D human skin equivalent model.

Main Results:

• Extracellular basic pH (>7.50) accelerated collagen breakdown by upregulating MMP-1 and downregulating COL1A1 via ROS and MAPK signaling.
• Acidic pH (<6.04) also induced slight MMP-1 upregulation and COL1A1 downregulation through ROS and the p38 pathway.
• Reactive oxygen species (ROS) and MAPK signaling pathways mediate pH-dependent collagen modulation.

Conclusions:

• Skin pH is a critical factor influencing collagen formation during wound healing.
• Findings support the development of novel therapeutic strategies targeting skin pH for enhanced wound repair.