Melatonin Accelerates Diabetic Wound Repair via Modulation of Tenascin C and Interleukin-10 in Fibroblasts

  • FASEB J. 2026 Jun 15;40(11):e72010. doi: 10.1096/fj.202600440RR.
Jingying Sun  1  2 ,  Yuqi Qian  1  2 ,  Sihan Chen  3 ,  Mi Zhou  1  2 ,  Yuanyang Yu  1  2  4 ,  Linlin Wang  1  2 ,  Xiaozhong Huang  4 ,  Xiong Chen  3 ,  Chunxiang Zhang  1  2  5 ,  Jia Sun  1  2
Affiliations
  • 1. Pediatric Research Institute, Pediatric Interdisciplinary Consortium, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2. Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, China.
  • 3. Center of Wound Repair and Regeneration, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 4. Department of Pediatric Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5. Department of Cardiology, the Affiliated Hospital of Southwest Medical University and Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research and Institute of Metabolic Diseases, Southwest Medical University, Luzhou, China.
PMID: 42233548 DOI: 10.1096/fj.202600440RR
Abstract

A central pathophysiological driver of chronic skin wounds in patients with diabetes and Other comorbidities is the dysregulation of the local wound microenvironment, characterized by compromised fibroblast functionality, insufficient extracellular matrix synthesis, and sustained inflammatory dysregulation. Previous studies have revealed that melatonin plays an indispensable role in safeguarding skin structural integrity and sustaining cutaneous homeostasis. However, the role of melatonin in chronic skin wounds associated with diabetes remains poorly understood. In this study, utilizing db/db mouse skin trauma models and in vitro cultures of human dermal fibroblasts (HDF) exposed to advanced glycation end products (AGEs), we established that melatonin robustly augmented granulation tissue formation in db/db mouse skin wounds, consequently expediting in vivo wound healing. Concomitantly, melatonin enhanced the wound reparative capacity of AGEs-treated HDF and stimulated fibroblast proliferation through canonical melatonin receptors (MT1/MT2), while abrogating their differentiation into myofibroblasts and mitigating pro-inflammatory responses. Moreover, RNA-sequencing and functional analyses elucidated that the pro-repair effects of melatonin on skin wounds were mechanistically linked to its modulation of tenascin C and interleukin-10. Collectively, this work thus paves the way for the translational application of melatonin in treating diabetic-associated chronic wounds.

Keywords
chronic skin wounds; diabetes; fibroblast; interleukin‐10; melatonin; tenascin C.
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