Wound healing can be divided into different phases, and timely initiation and cessation of these stages is key to successful wound healing; otherwise,
scar tissue forms in the wounded area.
Connexins (Cxs) were confirmed to influence
scar formation, and
Cx43, an indispensable member of the Cx family, was shown to be involved in this process. Our study investigated the regulatory role of
Cx43 in
scar formation and the possible cell signalling pathways. We established oral mucosa and skin wound healing models in C57BL/6J mice. RT-PCR, western blotting, immunohistochemistry and immunofluorescence were used to examine the expression of ECM components and key
proteins in cell signalling pathways (TGF-β1, Smad2/3,
Cx43, Erk1/2
MMP-1 and
collagen III). After injury, buccal mucosa
wounds healed with no
scar, whereas skin
wounds healed with an evident
scar. Nevertheless, TGF-β1 expression gradually increased by the 5th day after injury;
Cx43 expression showed a similar response, with a progressive increase in the skin and a peak on day 14. In contrast, TGF-β1 and
Cx43 expression in the oral mucosa remained low. The high level of TGF-β1 increased p-Smad2/3 levels and then induced
Cx43, whereas increased expression of
Cx43 antagonised the phosphorylation of Erk1/2, a
protein downstream of
Cx43, which affected MMP-1 synthesis. MMP-1 deficiency led to
collagen III accumulation and facilitated
scar formation. We demonstrated that TGF-β1-induced
Cx43 promotes
scar formation via the Erk/
MMP-1/
collagen III pathway.