2. Academic Validation
  3. P75NTR regulates autophagy through the YAP-mTOR pathway to increase the proliferation of interfollicular epidermal cells and promote wound healing in diabetic mice

P75NTR regulates autophagy through the YAP-mTOR pathway to increase the proliferation of interfollicular epidermal cells and promote wound healing in diabetic mice

  • Biochim Biophys Acta Mol Basis Dis. 2024 Jan 2:167012. doi: 10.1016/j.bbadis.2023.167012.
Zhenjie Wu 1,  Chunyan Liu 1,  Siyuan Yin 1,  Jiaxu Ma 2,  Rui Sun 2,  Guoqi Cao 2,  Yongpan Lu 3,  Jian Liu 1,  Linqi Su 1,  Ru Song 4,  Yibing Wang 5
Affiliations

Affiliations

  • 1 Department of Plastic Surgery, The First Affiliated Hospital of Shandong First, Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, PR China; Jinan Clinical Research Center for Tissue Engineering Skin Regeneration and Wound Repair, Jinan, Shandong 250014, PR China.
  • 2 Department of Plastic Surgery, The First Affiliated Hospital of Shandong First, Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, PR China; Department of Plastic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250012, PR China.
  • 3 Department of Plastic Surgery, The First Affiliated Hospital of Shandong First, Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, PR China; First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, PR China.
  • 4 Department of Plastic Surgery, The First Affiliated Hospital of Shandong First, Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, PR China; Jinan Clinical Research Center for Tissue Engineering Skin Regeneration and Wound Repair, Jinan, Shandong 250014, PR China. Electronic address: rusong_sdu@163.com.
  • 5 Department of Plastic Surgery, The First Affiliated Hospital of Shandong First, Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, PR China; Jinan Clinical Research Center for Tissue Engineering Skin Regeneration and Wound Repair, Jinan, Shandong 250014, PR China; Department of Plastic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250012, PR China; First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, PR China. Electronic address: ybwang@sdfmu.edu.cn.
PMID: 38176461 DOI: 10.1016/j.bbadis.2023.167012
Abstract

Wound healing is delayed in diabetic patients. Increased Autophagy and dysfunction of interfollicular epidermal (IFE) cells are closely associated with delayed healing of diabetic wounds. Autophagy plays an important role in all stages of wound healing, but its role in diabetic wound healing and the underlying molecular mechanisms are not clear. Here, we found that diabetic mice had delayed wound healing and increased Autophagy in wounds compared with normal mice and that chloroquine, an inhibitor of Autophagy, decreased the level of Autophagy, improved the function of IFE cells, and accelerated wound healing in diabetic mice. Treatment of IFE cells with advanced glycosylation end products (AGEs) resulted in increased microtubule-associated protein chain (LC3) expression and decreased prostacyclin-62 (p62) expression, indicating increased Autophagy in AGE-treated IFE cells. Moreover, P75NTR reduced Autophagy in IFE cells in the presence of AGEs and significantly increased the proliferation of IFE cells. In addition, P75NTR participated in regulating Autophagy in IFE cells and in wounds in diabetic mice through the YAP-mTOR signalling pathway, which increased the functional activity of the cells and the healing rate of wounds in diabetic mice. Thus, our study suggests that P75NTR protects IFE cells against AGEs by affecting Autophagy and accelerating wound healing in diabetic mice, providing a basis for understanding the role of Autophagy in diabetic wound healing.

Keywords

Autophagy; Diabetic wound; Interfollicular epidermal (IFE) cells; P75NTR.

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