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Endoplasmic reticulum stress response is induced by sulfur mustard in the mouse ear vesicant model
Author(s) -
Chang YokeChen,
Soriano Melannie,
Nguyen Michael,
Casillas Robert P,
Sabourin Carol L.,
Gordon Marion K.,
Gerecke Donald R.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.469.1
Subject(s) - endoplasmic reticulum , unfolded protein response , laminin , microbiology and biotechnology , downregulation and upregulation , extracellular matrix , chemistry , dermis , confocal microscopy , wound healing , biology , immunology , biochemistry , anatomy , gene
Time‐related changes in the histopathology of mouse skin occur 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. Grant Funding Source ES005022 , ES004738 , EY09056, and the NIH CounterACT Program through NIAMS U54AR055073