2. Academic Validation
  3. Omentin-1 promotes diabetic wound healing by regulating macrophage efferocytosis and M2 polarization

Omentin-1 promotes diabetic wound healing by regulating macrophage efferocytosis and M2 polarization

  • Int J Biol Macromol. 2026 Feb:347:150757. doi: 10.1016/j.ijbiomac.2026.150757.
Yumeng Huang 1,  Xiaofeng Ding 2,  Zheng Dong 3,  Youjun Ding 4,  Yutong Chen 3,  Haiting Zou 3,  Jingyi Chen 5,  Ping Yang 6,  Tianzhe Chen 3,  Zhouji Ma 7,  Qian Tan 8
Affiliations

Affiliations

  • 1 Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Clinical College, Jiangsu University, Nanjing, China.
  • 2 Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.
  • 3 Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
  • 4 Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Clinical College, Jiangsu University, Nanjing, China; Department of Emergency Surgery, The Fourth Affiliated Hospital of Jiangsu University (Zhenjiang Fourth People's Hospital), Zhenjiang, China.
  • 5 Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Clinical College, Nanjing University of Chinese Medicine, Nanjing, China.
  • 6 Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Department of Plastic and Reconstructive Surgery, Jinhu County People's Hospital, NO. 160, Shenhua Avenue, Jinhu County, Huai'an, Jiangsu, China.
  • 7 Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Soochow University, China.
  • 8 Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Clinical College, Jiangsu University, Nanjing, China; Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Clinical College, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: [email protected].
PMID: 41654047 DOI: 10.1016/j.ijbiomac.2026.150757
Abstract

Diabetes is a metabolic disorder that significantly impacts human health, with 25% of patients suffering from diabetic ulcers. Chronic persistent inflammation is one of the primary factors impeding wound healing in diabetes. As a recently identified adipocytokine, omentin-1 (also known as intelectin-1, ITLN1) demonstrates significant expression levels in the omentum, subcutaneous adipose tissue, and vascular endothelium, exhibiting potent anti-inflammatory characteristics. Emerging evidence indicates that this adipokine plays a crucial protective role in multiple inflammatory disorders, particularly in the pathogenesis of atherosclerosis, osteoarthritis, and inflammatory bowel disease. However, its therapeutic potential in diabetic wound healing remains unclear. Our experimental data demonstrated a marked downregulation of omentin-1 expression in cutaneous tissues obtained from the Streptozotocin (STZ)-induced diabetic murine model. Local administration of recombinant omentin-1 improved efferocytosis in impaired macrophages within the wound bed and promoted macrophage phenotypic switching to the reparative M2 phenotype, thereby attenuating inflammatory responses and accelerating wound healing in diabetic mice. Further mechanistic studies revealed that omentin-1 enhanced the expression of the key efferocytosis receptor MERTK (Mer proto-oncogene tyrosine kinase) in diabetic wounds and facilitated macrophage efferocytosis through modulation of the downstream Src/PI3K/Akt signaling cascade. Additionally, omentin-1 facilitated the polarization of macrophages toward the M2 phenotype and attenuated the inflammatory responses induced by lipopolysaccharide (LPS). The findings of this study indicate that omentin-1 suggests its potential as a candidate for developing novel adjunctive therapies for chronic non-healing diabetic wounds.

Keywords

Diabetic wound healing; Inflammation; M2 polarization; Macrophage efferocytosis; Omentin-1.

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