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Wound healing of cutaneous nitrogen mustard injuries by dynamic modulation of gap junction communication using connexin43 antisense oligodeoxynucleotides (216.6)
Author(s) -
Chang Yokechen,
Wang James,
Hahn Rita,
Chang HuiYing,
Gordon Marion,
Gerecke Donald
Publication year - 2014
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.28.1_supplement.216.6
Subject(s) - wound healing , keratinocyte , western blot , basement membrane , andrology , gap junction , medicine , biology , pathology , chemistry , immunology , microbiology and biotechnology , cell culture , intracellular , biochemistry , genetics , gene
Gap junction communication is tightly regulated in skin wound healing. Studies showed that targeting of connexin43 (Cx43) improves skin wound repair in diabetes. Vesicant induced skin injury results in dermal‐epidermal junction disruption and delayed wound repair. We treated Cx43 antisense oligodeoxynucleotides (asODN) on NM exposed SKH‐1 mouse dorsal skin to evaluate the wound healing response. We examined markers of basal keratinocytes, keratin5 (K5); epidermal differentiation, keratin10 (K10); proliferation, Ki67; and basement membrane, laminin 332 (LM332). Immunofluorescent (IF) studies showed reduced K5 expression, loss of K10 and Ki67, and an interrupted LM332 pattern of expression 1 day after NM exposure. By day 3, K10 reappeared in a diffuse pattern. By day 7, the LM332 appearance was thick and continuous. By day 10, there was intense expression of Ki67, accompanied by extreme hyperplasia. Animals treated with Cx43AsODN after NM exposure had an accelerated wound rate and improved reepithelialization so that the skin marker patterns above appeared at earlier timepoints. RT‐PCR and Western blot analysis showed significant reduction of Cx43 at days 3 and 7. IF studies also showed that Cx43 asODN treatment successfully reduced Cx43 expression and modulated higher Cx26 expression in the wound margin by day 3. The use of Cx43asODN may alter Cx expression and accelerate vesicant wound repair. Grant Funding Source : Supported by ES005022, EY09056, and NIAMS U54AR055073