Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, Los Angeles, United States; Weintraub Center for Reconstructive Biotechnology, Los Angeles, United States; Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, Los Angeles, United States; Weintraub Center for Reconstructive Biotechnology, Los Angeles, United States
Hiroko Okawa
Weintraub Center for Reconstructive Biotechnology, Los Angeles, United States; Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Miyagi, Japan
Takeru Kondo
Weintraub Center for Reconstructive Biotechnology, Los Angeles, United States; Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Miyagi, Japan
Daniel Khalil
Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, Los Angeles, United States
Lixin Wang
Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, Los Angeles, United States
Yvonne Roca
Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, Los Angeles, United States
Adam Clements
Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, Los Angeles, United States
Hodaka Sasaki
Weintraub Center for Reconstructive Biotechnology, Los Angeles, United States
Ella Berry
Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, Los Angeles, United States
Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, Los Angeles, United States
Attempts to minimize scarring remain among the most difficult challenges facing surgeons, despite the use of optimal wound closure techniques. Previously, we reported improved healing of dermal excisional wounds in circadian clock neuronal PAS domain 2 (Npas2)-null mice. In this study, we performed high-throughput drug screening to identify a compound that downregulates Npas2 activity. The hit compound (Dwn1) suppressed circadian Npas2 expression, increased murine dermal fibroblast cell migration, and decreased collagen synthesis in vitro. Based on the in vitro results, Dwn1 was topically applied to iatrogenic full-thickness dorsal cutaneous wounds in a murine model. The Dwn1-treated dermal wounds healed faster with favorable mechanical strength and developed less granulation tissue than the controls. The expression of type I collagen, Tgfβ1, and α-smooth muscle actin was significantly decreased in Dwn1-treated wounds, suggesting that hypertrophic scarring and myofibroblast differentiation are attenuated by Dwn1 treatment. NPAS2 may represent an important target for therapeutic approaches to optimal surgical wound management.
