mustard in the mouse ear vesicant model
Chang, Y-C., Soriano, M., Nguyen, M., Casillas, R. P., Sabourin, C. L., Gordon, M. K., Gerecke, D. R.
after topical exposure to the vesicant agent, bis(2-chloroethyl)
sulfide (SM) using the mouse ear vesicant model (MEVM). Some
of these changes include increasing edema, detachment of the
epidermis from the dermis, and upregulation of laminin-332.
Endoplasmic reticulum stress response (ESR) was observed by
confocal microscopy. Microarray analysis and RT-PCR
experiments indicated there was upregulation of several heat shock
proteins and folding chaperones such glucose-regulated protein 78
and GRP94 in the ER. It confirmed the confocal observations and
suggested that ER stress occurs very quickly in the MEVM. The
accumulation of laminin γ2 protein, one of the chains of laminin-
332, in the ER was visualized by confocal microscopy and co
localized with the ER chaperones. This accumulation appeared
specifically in the migrating, but not proliferating cells. These
observations are consistent with recent reports that laminin-332 is
found in migrating, transformed epithelial cells that have left the
cell cycle, but not in proliferating cells. These results suggest that
laminin γ2 is misfolded after SM treatment, resulting in decreased
secretion and reduced overall amounts of laminin-332 in the
extracellular matrix. This would explain the observation that there
is a delayed wound healing response evident in this wound model.