Thiomyristoyl promotes type 2 diabetic wound healing and inhibits scarring via the PPARγ/Sirt3/SOD2 axis

  • Free Radic Biol Med. 2026 Jun 8:254:31-45. doi: 10.1016/j.freeradbiomed.2026.06.016.
Xiuyu Ge  1 ,  Ziyue Ye  1 ,  Haozhi Qin  1 ,  Chaochao Yuan  2 ,  Yixiang Han  2 ,  Ying Gao  3 ,  Yan Shen  4 ,  Weiwei Chu  5 ,  Jing Xu  6
Affiliations
  • 1. Department of Plastic Surgery and Burn, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China; Central Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China.
  • 2. Department of Plastic Surgery and Burn, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China.
  • 3. Department of Anesthesiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China.
  • 4. Department of Prevention and Health Care, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China. Electronic address: [email protected].
  • 5. Department of Plastic Surgery and Burn, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China; Central Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China. Electronic address: [email protected].
  • 6. Department of Plastic Surgery and Burn, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China; Central Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233000, China. Electronic address: [email protected].
PMID: 42264197 DOI: 10.1016/j.freeradbiomed.2026.06.016
Abstract

Fibroblasts are essential for the process of wound healing. However, under diabetic conditions, they often exhibit functional impairment and fibrosis, leading to impaired healing. Currently, there are limited effective interventions for fibroblast dysfunction. Through preliminary screening of small-molecules, Thiomyristoyl(TM), which enhances cellular plasticity and possesses anti-fibrotic properties, was selected for this research to investigate its involvement and mechanism in the wound healing process in type 2 diabetes. Experimental results indicated that wound healing was delayed in diabetic mice, accompanied by reduced cell proliferation and significant fibrosis. Under high glucose conditions, mouse dermal fibroblasts (MDFs) exhibited decreased viability, proliferation, and migration, accompanied by excessive accumulation of Reactive Oxygen Species (ROS). TM intervention effectively restored the multi-differentiation potential of MDFs and ameliorated the aforementioned cellular functional impairments. Transcriptome analysis and related experiments indicated that TM upregulates SIRT3 expression via the PPARγ signaling pathway, reduces the acetylation level of superoxide dismutase 2 (SOD2), thereby alleviating oxidative stress and inhibiting the expression of fibrosis-related proteins. The strategy of activating the PPARγ/SIRT3/SOD2 axis with TM provides a potential therapeutic target for treating diabetic wounds.

Keywords
Dermal fibroblasts; Dermal stem cells; Diabetic wound; PPARγ; Thiomyristoyl.
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