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<p>Diabetic foot ulcers are severe diabetic complications, and promoting impaired angiogenesis is essential for wound healing. Pro-angiogenic galectin-3 is elevated in diabetic serum and promotes systemic insulin resistance that may impair wound healing. However, the exact role of galectin-3 in the regulation of diabetic wound healing remains unclear. Here, we demonstrate that galectin-3 promotes skin wound healing and angiogenesis via binding to its receptor integrin α5β1, and enhances downstream focal adhesion kinase phosphorylation by forming a liquid-liquid phase separation with integrin α5β1. Under diabetic conditions, aberrant accumulated advanced glycation end-products bind to galectin-3, blocking its interaction with integrin α5β1 and impairing angiogenesis. Topical treatment of recombinant galectin-3 in hydrogels promotes diabetic wound healing in rodents without causing systemic insulin resistance and synergizes with insulin. This study clarifies the binding of galectin-3 to integrin α5β1, instead of advanced glycation end-products, forming phase separation to promote angiogenesis and diabetic wound healing, laying the foundation for local galectin-3 therapy to treat diabetic foot ulcers.</p>

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Galectin-3-integrin α5β1 phase separation disrupted by advanced glycation end-products impairs diabetic wound healing in rodents

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月7日

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  • Zhongyu Zhang,
  • Zhengde Zhao,
  • Xiuyi Huang,
  • Lifang Zhou,
  • Xin Jiang,
  • Haoliang Wu,
  • Chenshu Liu,
  • Kan Huang,
  • Jielu Wen,
  • Yunchong Liu,
  • Michelle C. Miller,
  • Zihan Zhao,
  • Zhen He,
  • Yuxin Wang,
  • Siyu Liu,
  • Lijin Huang,
  • Lining Yuan,
  • Renli Zeng,
  • Zhipeng Cen,
  • Anning Chen,
  • Yanbo Chen,
  • Gang Zeng,
  • Wenzhou Liu,
  • Xiaosi Hong,
  • Meng Ren,
  • Li Yan,
  • Yang Zhang,
  • Dongxian Guan,
  • Xiaoyu Tian,
  • Weikang Cai,
  • Guihua Tai,
  • Kevin H. Mayo,
  • Yifa Zhou,
  • Zilun Li,
  • Sifan Chen

摘要

Diabetic foot ulcers are severe diabetic complications, and promoting impaired angiogenesis is essential for wound healing. Pro-angiogenic galectin-3 is elevated in diabetic serum and promotes systemic insulin resistance that may impair wound healing. However, the exact role of galectin-3 in the regulation of diabetic wound healing remains unclear. Here, we demonstrate that galectin-3 promotes skin wound healing and angiogenesis via binding to its receptor integrin α5β1, and enhances downstream focal adhesion kinase phosphorylation by forming a liquid-liquid phase separation with integrin α5β1. Under diabetic conditions, aberrant accumulated advanced glycation end-products bind to galectin-3, blocking its interaction with integrin α5β1 and impairing angiogenesis. Topical treatment of recombinant galectin-3 in hydrogels promotes diabetic wound healing in rodents without causing systemic insulin resistance and synergizes with insulin. This study clarifies the binding of galectin-3 to integrin α5β1, instead of advanced glycation end-products, forming phase separation to promote angiogenesis and diabetic wound healing, laying the foundation for local galectin-3 therapy to treat diabetic foot ulcers.