Role of Tissue-Type Plasminogen Activator in Salicylic Acid–Induced Sloughing of Human Corn Tissue

Abstract

Background: Plasminogen activators (PAs) and their regulatory counterparts, PA inhibitors (PAIs), play a role in normal differentiation processes and various pathophysiologic conditions of the epidermis. Normal desquamation of corneocytes from the skin3s surface may, in part, be regulated by the balanced activities of tissue-type PA (tPA) and PAI-2. Salicylic acid (SA) is commonly used to remove the hyperkeratotic tissue of corns, calluses, and verrucae, and it may disrupt intercellular adhesion structures; however, its exact mechanism of keratolytic action is poorly defined. We sought to determine the effects of SA by comparing the levels of PA and PAI messenger RNA (mRNA) in normal skin, untreated corns, and SA-treated corns. Methods: Untreated and SA-treated human corn tissue samples were obtained from patients electing surgery to repair bony defects that underlay their lesions. Histopathologic examination of corns was performed by staining the tissue sections with hematoxylin and eosin and by light microscopy. Polymerase chain reaction was used to compare mRNA expression of PAs and PAIs in normal skin, untreated corns, and SA-treated corns. Results: We demonstrated lower tPA and higher PAI-2 mRNA levels in corn tissue compared with normal skin. In corn tissue treated with SA, the expression of tPA mRNA increased and of PAI-2 mRNA decreased to the levels found in normal skin. Conclusion: An altered balance in tPA and PAI-2 levels contributes to the induction of hyperkeratotic corn tissue and suggests that the keratolytic action of SA is associated with its ability to stimulate proteinase-meditated desquamation processes. (J Am Podiatr Med Assoc 98(5): 345–352, 2008)