Electrical Stimulation Using a Low-Frequency and Low-Intensity Alternating Current Modulates Type I Procollagen Production and MMP-1 Expression in Dermal Fibroblasts
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Background: Despite various therapeutic modalities for keloids have been introduced; how- ever, their therapeutic effects are limited. Therefore, the development of a new approach for inhibiting collagen production by scar fibroblasts is needed. Objective: To investigate the effect of electrical stimulation using a low-frequency and low-in- tensity alternating current on collagen and MMP-1 levels in human dermal fibroblasts. Methods: Low-frequency (20 kHz) and low-intensity (1 V/cm) electrical stimulations were applied to primary dermal fibroblasts. The production of type I procollagen and expression of matrix metalloproteinase-1 were evaluated. Transcriptomic analyses were conducted to explore the possible modes of action of electrical stimulation. Results: Electrical stimulation effectively suppressed type I procollagen production and increased MMP-1 expression. In addition, transcriptomic analyses revealed that electrical stimu- lation altered the gene expression associated with membrane permeability and the structure of cellular membranes. Validation using real-time polymerase chain reaction revealed that electri- cal stimulation significantly altered the expression of mechanosensitive ion channels (PIEZO2) and membrane-bound protein organizing caveolae (CAVIN2). Conclusion: Electrical stimulation using low-frequency and low-intensity alternating currents effectively modulates extracellular matrix homeostasis by altering the cellular membrane struc- ture and function. Our findings suggest a promising therapeutic approach for the management of keloids and hypertrophic scars.
Abstract
Background: Despite various therapeutic modalities for keloids have been introduced; how- ever, their therapeutic effects are limited. Therefore, the development of a new approach for inhibiting collagen production by scar fibroblasts is needed. Objective: To investigate the effect of electrical stimulation using a low-frequency and low-in- tensity alternating current on collagen and MMP-1 levels in human dermal fibroblasts. Methods: Low-frequency (20 kHz) and low-intensity (1 V/cm) electrical stimulations were applied to primary dermal fibroblasts. The production of type I procollagen and expression of matrix metalloproteinase-1 were evaluated. Transcriptomic analyses were conducted to explore the possible modes of action of electrical stimulation. Results: Electrical stimulation effectively suppressed type I procollagen production and increased MMP-1 expression. In addition, transcriptomic analyses revealed that electrical stimu- lation altered the gene expression associated with membrane permeability and the structure of cellular membranes. Validation using real-time polymerase chain reaction revealed that electri- cal stimulation significantly altered the expression of mechanosensitive ion channels (PIEZO2) and membrane-bound protein organizing caveolae (CAVIN2). Conclusion: Electrical stimulation using low-frequency and low-intensity alternating currents effectively modulates extracellular matrix homeostasis by altering the cellular membrane struc- ture and function. Our findings suggest a promising therapeutic approach for the management of keloids and hypertrophic scars.