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.


METHODS
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.


CONCLUSIONS
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.
Cirillo
N
N
Regional Center on Craniofacial Malformations-MRI, Department of Odontostomatology, 1st School of Medicine and Surgery, II University of Naples, Naples, Italy. nicola.cirillo@unina2.it
Femiano
F
F
Gombos
F
F
Lanza
A
A
D017209:Apoptosis; D015153:Blotting, Western; D002461:Cell Line, Transformed; D051184:Desmoglein 3 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019311:Staurosporine / Q000494:pharmacology
D051184:Desmoglein 3; D004791:Enzyme Inhibitors; D020780:Matrix Metalloproteinase 9; D019311:Staurosporine