Spatiotemporal Adaptations-Driven Dynamic Thra Activation Simulates a Skin Wound Healing Response

Area of Science:

• Molecular biology
• Regenerative medicine
• Endocrinology

Background:

• Skin wound repair involves sequential epidermal and dermal phases.
• The molecular mechanisms coordinating these phases and the role of endocrine receptors are not fully understood.

Purpose of the Study:

• To identify critical hormone receptors regulating spatiotemporal skin regeneration.
• To elucidate the role of thyroid hormone receptor alpha (Thra) in wound healing phases.

Main Methods:

• Bulk and single-cell RNA sequencing
• Spatial transcriptomics
• In vivo and in vitro analyses in mouse models (hyper/hypothyroidism, wound models)
• Skin organoid models

Main Results:

• Thra acts as a key regulator of phase-coupled skin regeneration.
• Epidermal Thra activates glutathione metabolism (via GGCT) for reepithelialization.
• Dermal Thra mediates SAA3-FN1 interaction for matrix maturation and angiogenesis.

Conclusions:

• Thra orchestrates distinct, coordinated mechanisms in epidermal and dermal wound healing phases.
• Thra is essential for spatiotemporal adaptability in skin repair.
• Findings offer insights for clinical strategies to improve wound healing.