Expression and function of connexin 43 in XXXX gingival wound healing and fibroblasts.

@entity1 @entity32 @entity7 @entity33 @entity11346 @entity2533 @entity3419 @entity35466
Connexins (C*s) are a family of transmembrane proteins that form hemichannels and gap junctions (GJs) on the cell membranes, and transfer small signaling molecules between the cytoplasm and extracellular space and between connecting cells, respectively. Among C*s, suppressing C*43 expression or function promotes skin wound closure and granulation tissue formation, and may alleviate scarring, but the mechanisms are not well understood. Oral @entity33 is characterized by faster wound closure and scarless wound healing outcome as compared to skin wounds. Therefore, we hypothesized that C*43 function is down regulated during @entity1 gingival wound healing, which in fibroblasts promotes expression of genes conducive for fast and scarless wound healing. Cultured gingival fibroblasts expressed C*43 as their major connexin. Immunostaining of unwounded @entity1 gingiva showed that C*43 was abundantly present in the epithelium, and in connective tissue formed large C*43 plaques in fibroblasts. At the early stages of wound healing, C*43 was strongly down regulated in wound epithelial cells and fibroblasts, returning to the level of normal tissue by day 60 post-wounding. Blocking of C*43 function by C*43 mimetic peptide Gap27 suppressed GJ-mediated dye transfer, promoted migration, and caused significant changes in the expression of wound healing-associated genes in gingival fibroblasts. In particular, out of 54 genes analyzed, several MMPs and @entity2533 , involved in regulation of @entity32 and extracellular matrix (ECM) turnover, and @entity7 , involved in angiogenesis, were significantly upregulated while pro-fibrotic ECM molecules, including Collagen type I, and cell contractility-related molecules were significantly down regulated. These responses involved MAPK, @entity35466 /b and @entity2533 signaling pathways, and @entity11346 and @entity3419 transcription factors. Thus, suppressed function of C*43 in fibroblasts promotes their migration, and regulates expression of wound healing-associated genes via @entity11346 , @entity3419 , MAPK, @entity35466 /b and @entity2533 signaling pathways, and may promote fast and scarless wound healing in @entity1 gingiva.
