Journal
EXPERIMENTAL CELL RESEARCH
Volume 367, Issue 2, Pages 150-161Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2018.03.031
Keywords
Skin; Gingiva; Fibroblasts; Connexin 43; Gap junctions; Hemichannels
Categories
Funding
- Canadian Institutes of Health Research [MOP-77550, PJT-153223]
- Natural Sciences and Engineering Research Council of Canada [RGPIN-2017-05765]
- National Institute of Health [CA196214]
- Welch Foundation Grant [AQ-1507]
- UBC Faculty of Dentistry Graduate Awards
- NATIONAL CANCER INSTITUTE [R01CA196214] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [R01EY012085] Funding Source: NIH RePORTER
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Fibroblasts are the most abundant connective tissue cells and play an important role in wound healing. It is possible that faster and scarless wound healing in oral mucosal gingiva relative to skin may relate to the distinct phenotype of the fibroblasts residing in these tissues. Connexin 43 (Cx43) is the most ubiquitous Cx in skin (SFBLs) and gingival fibroblasts (GFBLs), and assembles into hemichannels (HCs) and gap junctions (GJs) on the cell membrane. We hypothesized that SFBLs and GFBLs display distinct expression or function of Cx43, and that this may partly underlie the different wound healing outcomes in skin and gingiva. Here we show that Cx43 distinctly formed Cx43 GJs and HCs in human skin and gingiva in vivo. However, in SFBLs, in contrast to GFBLs, only a small proportion of total Cx43 assembled into HC plaques. Using an in vivo-like 3D culture model, we further show that the GJ, HC, and channel-independent functions of Cx43 distinctly regulated wound healing related gene expression in GFBLS and SFBL5. Therefore, the distinct wound healing outcomes in skin and gingiva may partly relate to the inherently different assembly and function of Cx43 in the resident fibroblasts.
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