posted on 2023-12-08, 18:37authored byYuxin Xiang, Yuhong Jiang, Lei Lu
The
management of wounds remains a significant healthcare
challenge,
highlighting the need for effective wound healing strategies. To address
this, it is crucial to explore the molecular mechanisms underlying
tissue repair as well as explore potential therapeutic approaches.
Trypsin, as a serine protease, has been clinically utilized for wound
healing for decades; however, it still lacks systemic investigation
on its role and related mechanism. This study aimed to investigate
the effects of low-dose trypsin on wound healing both in vitro and in vivo. While trypsin is an endogenous stimulus
for protease-activated receptor 2 (PAR2), we discovered that both
low-dose trypsin and synthesized PAR2 agonists significantly enhanced
the migration, adhesion, and proliferation of fibroblasts and macrophages,
similar to the natural repair mechanism mediated by mast cell tryptase.
Moreover, such cell functions induced by trypsin were largely inhibited
by PAR2 blockade, indicating the participation of trypsin via PAR2 activation. Additionally, low-dose trypsin notably
expedited healing and regeneration while enhancing collagen deposition
in skin wounds in vivo. Importantly, upon stimulation
of trypsin or PAR2 agonists, there were significant upregulations
of genes including claudin-7 (Cldn7), occludin (Ocln), and interleukin-17A
(IL-17A) associated with proliferation and migration, extracellular
matrix (ECM), tight junction, and focal adhesion, which contributed
to wound healing. In summary, our study suggested that a low-dose
trypsin could be a promising strategy for wound healing, and its function
was highly dependent on PAR2 activation.