Metalloproteinase 9 is the outer executioner of desmoglein 3 in apoptotic keratinocytes

OBJECTIVE: To investigate the specific matrix metalloproteinases (MMPs) targeting desmoglein 3 (Dsg3) in apoptotic keratinocytes. METHOD: Inhibitor studies on cultured keratinocytes and Western blot analysis. RESULTS: Blocking of MMP-9 activity strongly reduces shedding of Dsg3 from cell surface. MMP-2 has a less relevant role in the cleavage of Dsg3 while other MMPs, such as MMP-1, -3, and -8, do not target Dsg3. CONCLUSION: Apoptic keratinocytes impair the extracellular domain of cell surface Dsg3 by MMP-9 activity. The discovery of a specific targeting of Dsg3 could be useful to understand the pathophysiology of diseases in which Dsg3 is affected.