YAP promotes wound healing in diabetic mice by improving endothelial cell function via the regulation of SEMA3B
- Acta Histochem. 2026 Apr 27;128(3):152335. doi: 10.1016/j.acthis.2026.152335.
- 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; Department of Plastic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250012, PR China.
- 2. Department of Burns and Wound Repair, The First Affiliated Hospital of Shandong Second Medical University, Weifang People's Hospital, Weifang, Shandong, 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; Jinan Clinical Research Center for Tissue Engineering Skin Regeneration and, Wound Repair, Jinan, Shandong 250014, 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; First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, PR China.
- 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: [email protected].
Impaired angiogenesis is a critical factor contributing to delayed wound healing in diabetes patients. This study aimed to investigate the role and underlying mechanism of semaphorin 3B (SEMA3B) and its upstream regulator Yes-associated protein (YAP) in diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were treated with advanced glycation end products (AGEs) to simulate a diabetic environment in vitro. AGEs significantly suppressed the viability, proliferation, and tube formation capacity of HUVECs, which was accompanied by downregulated expression of both SEMA3B and YAP. Consistent with these results, decreased expression of SEMA3B and YAP was detected in the skin and wound tissues of diabetic mice. Overexpression of SEMA3B significantly reversed AGE-induced endothelial dysfunction. Mechanistically, YAP was identified as a positive regulator of SEMA3B transcription. Overexpression of YAP restored endothelial function through the upregulation of SEMA3B, whereas YAP inhibition exacerbated functional impairment. In vivo experiments demonstrated that topical application of a YAP Inhibitor delayed wound healing in diabetic mice concomitant with reduced SEMA3B expression. Furthermore, topical application of recombinant semaphorin 3B protein (rSEMA3B) significantly promoted wound healing in diabetic mice, confirming its therapeutic effect. This study reveals the crucial regulatory role of the YAP/SEMA3B axis in diabetic wound healing, demonstrating that YAP improves endothelial function and promotes angiogenesis by upregulating SEMA3B, thereby accelerating wound closure. These findings suggest a novel potential therapeutic target for the treatment of diabetic wounds.
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Research Areas: Cancer
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