Early-stage pressure ulcers are treatable and reversible, an advanced stage pressure ulcer is associated with significant patient mortality and have a deleterious impact on patient's quality of life. Acid-sensing ion channel 3 (ASIC3) is a crucial neural sensor for extracellular protons produced in sensory neurons. ASIC3 is a sensitive neuronal mechanosensor for directing pressure vital to the vasodilation response, which helps prevent aggravation of pressure ulcers. In this study, we adopted a mouse model of ischemic pressure ulcers to sequentially analyze the effect of pressure load to induce early-stage pressure ulcer and activation of ASIC3. A sterile magnet sized 10 × 10 × 1 mm3 was placed above the gluteus muscle of BALB/c-nu nude mice, and another magnet was placed directly above the implanted surface at regular intervals. To validate the pressure ulcer model, we repeated cyclic application of the magnet and loaded pressure to induce ischemia-perfusion injury similar to clinical situation. The established murine model of pressure ulcer is evaluated by histological and molecular analysis to stage the ulcer relevant to human patients. We have detected that significant activation of mRNA and protein levels of ASIC3 after 45 min of pressure load and subsequent increase in calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) transcription as a protective mechanism against a local pressure load. Additionally, increase in transient receptor potential cation channel subfamily V member 1 (TRPV1) transcription was observed, further potentiating the increase in mRNA expressions of IL-6 and TNF-α. Finally, the expression of ASIC3 and TRPV1 increased in the mouse epidermis, which peaked at 60 min and gradually decreased afterward. Our findings suggest that ASIC3 may serve as a biomarker and potential therapeutic target to detect early changes of pressure ulcer.

LB007 - Activation of ASIC3 induces pressure-mediated ischemia in a mouse model of skin pressure ulcer

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