Actions of the sulfur mustard analogue, nitrogen mustard, on mouse skin and post exposure treatment with Connexin 43 antisense oligodeoxynucleotides
Citation & Export
Hide
Simple citation
Wang, James Daniel.
Actions of the sulfur mustard analogue, nitrogen mustard, on mouse skin and post exposure treatment with Connexin 43 antisense oligodeoxynucleotides. Retrieved from
https://doi.org/doi:10.7282/T30K26VD
Export
Description
TitleActions of the sulfur mustard analogue, nitrogen mustard, on mouse skin and post exposure treatment with Connexin 43 antisense oligodeoxynucleotides
Date Created2014
Other Date2014-05 (degree)
Extentxiii, 165 p. : ill.
DescriptionNitrogen mustard (NM), a less potent vesicant analog of sulfur mustard (SM), has very similar biological activity and function compared with SM. Connexin 43 (Cx43), the ubiquitously expressed gap junction protein in the skin, plays a significant regulatory role in wound repairs. In non-diabetic rodents and humans, there is a downregulation of Cx43 and an up-regulation of Connexin 26 and 30 (Cx26 and Cx30) in keratinocytes at the wound edges. The SKH-1 hairless mouse is a widely used wound healing model which has been used in SM research. The studies described here employed this model to examine the hypothesis that the changes in expression of Cx43 which are involved in diabetic and incisional/excisional wound healing play a role in the healing of NM chemical burn injuries as well. In addition, we hypothesize that Cx43 antisense oligodeoxynucleotides (Cx43 asODN) will facilitate the healing process after NM exposure as has been observed in the treatment of diabetic and incisional/excisional wounds. Using the SKH-1 mouse dorsal skin model, the present studies demonstrated that Cx43 was downregulated by NM at days 1, 3, 7, and 10 post-NM exposure, in a manner similar to that normally occurring in excisional/incisional wounds. In addition, Cx43 was further downregulated significantly by Cx43 asODN at day 3 and day 7. In iii contrast, Cx26 and Cx30 were upregulated by NM for days 1, 3, 7, and 10 just has been observed in the diabetic and incisional/excisional wound models. In addition, Cx43 asODN significantly reduced expression of Cx26 and Cx30. Furthermore, Cx43 asODN reduced levels of the proinflammatory mediator interleukin 1B (IL-1B), COX-2 and increased interleukin 10 (IL-10), an anti-inflammatory cytokine. Finally, the histological examination of tissue sections of the mouse skin demonstrated that Cx43 asODN reduced inflammatory cell infiltration, hyperplasia, and thickening of the stratum corneum. The data suggest that Cx43, Cx26, and Cx30 play important roles in the healing of NM injuries in the SKH-1 hairless mouse dorsal skin model similar to that of the incisional/excisional wound model. In addition, post exposure treatment with Cx43 asODN leads to reduce expression of Cx43, Cx26, and Cx30 and facilitate wound repair.
NoteM.S.
NoteIncludes bibliographical references
Noteby James Daniel Wang
Genretheses, ETD graduate
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.