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Acute Inhibition of Connexin43 Expression Promotes Vesicant Wound Repair in a Nitrogen Mustard Induced Hairless Mouse Cutaneous Injury Model
Author(s) -
Chang Yoke-Chen,
Wang James D,
Hahn Rita A,
Gordon Marion K,
Gerecke Donald R
Publication year - 2012
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.26.1_supplement.916.2
Subject(s) - hairless , wound healing , inflammation , proinflammatory cytokine , immune system , cytokine , medicine , western blot , immunology , pharmacology , chemistry , andrology , biochemistry , gene
The gap‐junction proteins, the connexins, mediate intercellular communication and play a significant regulatory role in wound repairs. Recent studies showed that transient inhibition of connexin43 (Cx43) expression resulted in accelerated wound healing in both incisional and burn skin wounds. Skin wounds caused by vesicants generally result in an acute immune response and delayed wound repairs. We tested Cx43 antisense oligodeoxynucleotides (asODN) in a time course study of SKH‐1 mouse skin injury induced by the vesicant, nitrogen mustard, to observe the wound repair response. Animals treated with asODN had a significantly improved survival rate after 10 days when compared to all other control groups. Histological examination of tissue sections showed less acute inflammation for the asODN treated group when compared to the control groups. RT‐PCR and Western blot analysis showed a reduction of Cx43 for days 1 and 3. Cx 26 and 30 were also reduced at days 1 and 3 as shown by RT‐PCR. IL1B, the proinflammatory cytokine is five times less in the asODN samples compared to NM alone. IL10, the anti‐inflammatory cytokine is three fold higher compared to NM alone at three days post exposure. Macrophage elastase decreased at days 7 and 10 when compared to NM alone. This suggests Cx43 is essential to wound repair signaling. The potential use of Cx43 asODN helped reduction in secondary damage and a promotion of vesicant wound repair. Grant Funding Source : ES005022 , ES004738 , EY09056, and NIAMS U54AR055073