Low-Dose Trypsin Accelerates Wound Healing via Protease-Activated Receptor 2.

Area of Science:

• Biochemistry
• Cell Biology
• Dermatology

Background:

• Wound management presents a significant healthcare challenge, necessitating novel therapeutic strategies.
• Trypsin, a serine protease, has historical clinical use in wound healing but lacks comprehensive mechanistic understanding.
• Investigating molecular mechanisms of tissue repair is crucial for developing effective wound healing interventions.

Purpose of the Study:

• To elucidate the effects of low-dose trypsin on wound healing processes.
• To investigate the role of protease-activated receptor 2 (PAR2) in trypsin-mediated wound repair.
• To explore the molecular pathways involved in trypsin-enhanced wound healing.

Main Methods:

• In vitro studies assessed fibroblast and macrophage responses to low-dose trypsin and PAR2 agonists.
• In vivo experiments evaluated the efficacy of low-dose trypsin in promoting skin wound healing and regeneration.
• Gene expression analysis identified key molecular players, including claudin-7 (Cldn7), occludin (Ocln), and interleukin-17A (IL-17A).

Main Results:

• Low-dose trypsin and PAR2 agonists significantly enhanced fibroblast and macrophage migration, adhesion, and proliferation.
• Trypsin-induced cellular functions were largely dependent on PAR2 activation, as evidenced by inhibition studies.
• In vivo, low-dose trypsin accelerated wound healing, promoted regeneration, and increased collagen deposition.

Conclusions:

• Low-dose trypsin represents a promising therapeutic strategy for enhancing wound healing.
• The wound healing effects of trypsin are primarily mediated through the activation of protease-activated receptor 2 (PAR2).
• Upregulation of specific genes involved in cell proliferation, migration, extracellular matrix, and tight junctions contributes to trypsin's efficacy.