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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
International journal of molecular sciences
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40806291/ |
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| _version_ | 1868266165161164801 |
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| author | Tadese, Dawit Adisu Mwangi, James Michira, Brenda B Wang, Yi Cao, Kaixun Yang, Min Khalid, Mehwish Wang, Ziyi Lu, Qiumin Lai, Ren |
| author_facet | Tadese, Dawit Adisu Mwangi, James Michira, Brenda B Wang, Yi Cao, Kaixun Yang, Min Khalid, Mehwish Wang, Ziyi Lu, Qiumin Lai, Ren Tadese, Dawit Adisu Mwangi, James Michira, Brenda B Wang, Yi Cao, Kaixun Yang, Min Khalid, Mehwish Wang, Ziyi Lu, Qiumin Lai, Ren |
| collection | PubMed - marine biology |
| contents | D-Tryptophan Promotes Skin Wound Healing via Extracellular Matrix Remodeling in Normal and Diabetic Models. Tadese, Dawit Adisu Mwangi, James Michira, Brenda B Wang, Yi Cao, Kaixun Yang, Min Khalid, Mehwish Wang, Ziyi Lu, Qiumin Lai, Ren Animals Wound Healing Diabetes Mellitus, Experimental Mice Extracellular Matrix Tryptophan Male Hypoxia-Inducible Factor 1, alpha Subunit Skin Mice, Inbred C57BL Disease Models, Animal Apoptosis Vascular Endothelial Growth Factor A Diabetic wounds are a devastating complication that cause chronic pain, recurrent infections, and limb amputations due to impaired healing. Despite advances in wound care, existing therapies often fail to address the underlying molecular dysregulation, highlighting the need for innovative and safe therapeutic approaches. Among these, D-amino acids such as D-tryptophan (D-Trp) have emerged as key regulators of cellular processes; however, their therapeutic potential in diabetic wounds remains largely unexplored. Here, we investigate the therapeutic potential of D-Trp in streptozotocin (STZ)-induced diabetic mice, comparing it with phosphate-buffered saline (PBS) controls and vascular endothelial growth factor (VEGF) as a positive control. Wound healing, inflammation, and histopathology were assessed. Protein and gene expression were analyzed via Western blot and RT-qPCR, respectively. Biolayer interferometry (BLI) measured the binding of D-Trp to hypoxia-inducible factor-1α (HIF-1α). D-Trp accelerated wound healing by modulating extracellular matrix (ECM) remodeling, signaling, and apoptosis. It upregulated matrix metalloproteinases (MMP1, MMP3, MMP-9), Janus kinase 2 (JAK2), and mitogen-activated protein kinase (MAPK) proteins while reducing pro-inflammatory cytokines (tumor necrosis factor-α [], interleukin-1β [], ). D-Trp also suppressed caspase-3 and enhanced angiogenesis through HIF-1α activation. These findings suggest that D-Trp promotes healing by boosting ECM turnover, reducing inflammation, and activating MAPK/JAK pathways. Thus, D-Trp is a promising therapeutic for diabetic wounds. |
| format | Artículo científico |
| id | pubmed_40806291 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | International journal of molecular sciences |
| record_format | pubmed |
| spellingShingle | D-Tryptophan Promotes Skin Wound Healing via Extracellular Matrix Remodeling in Normal and Diabetic Models. Tadese, Dawit Adisu Mwangi, James Michira, Brenda B Wang, Yi Cao, Kaixun Yang, Min Khalid, Mehwish Wang, Ziyi Lu, Qiumin Lai, Ren Animals Wound Healing Diabetes Mellitus, Experimental Mice Extracellular Matrix Tryptophan Male Hypoxia-Inducible Factor 1, alpha Subunit Skin Mice, Inbred C57BL Disease Models, Animal Apoptosis Vascular Endothelial Growth Factor A D-Tryptophan Promotes Skin Wound Healing via Extracellular Matrix Remodeling in Normal and Diabetic Models. Tadese, Dawit Adisu Mwangi, James Michira, Brenda B Wang, Yi Cao, Kaixun Yang, Min Khalid, Mehwish Wang, Ziyi Lu, Qiumin Lai, Ren Animals Wound Healing Diabetes Mellitus, Experimental Mice Extracellular Matrix Tryptophan Male Hypoxia-Inducible Factor 1, alpha Subunit Skin Mice, Inbred C57BL Disease Models, Animal Apoptosis Vascular Endothelial Growth Factor A Diabetic wounds are a devastating complication that cause chronic pain, recurrent infections, and limb amputations due to impaired healing. Despite advances in wound care, existing therapies often fail to address the underlying molecular dysregulation, highlighting the need for innovative and safe therapeutic approaches. Among these, D-amino acids such as D-tryptophan (D-Trp) have emerged as key regulators of cellular processes; however, their therapeutic potential in diabetic wounds remains largely unexplored. Here, we investigate the therapeutic potential of D-Trp in streptozotocin (STZ)-induced diabetic mice, comparing it with phosphate-buffered saline (PBS) controls and vascular endothelial growth factor (VEGF) as a positive control. Wound healing, inflammation, and histopathology were assessed. Protein and gene expression were analyzed via Western blot and RT-qPCR, respectively. Biolayer interferometry (BLI) measured the binding of D-Trp to hypoxia-inducible factor-1α (HIF-1α). D-Trp accelerated wound healing by modulating extracellular matrix (ECM) remodeling, signaling, and apoptosis. It upregulated matrix metalloproteinases (MMP1, MMP3, MMP-9), Janus kinase 2 (JAK2), and mitogen-activated protein kinase (MAPK) proteins while reducing pro-inflammatory cytokines (tumor necrosis factor-α [], interleukin-1β [], ). D-Trp also suppressed caspase-3 and enhanced angiogenesis through HIF-1α activation. These findings suggest that D-Trp promotes healing by boosting ECM turnover, reducing inflammation, and activating MAPK/JAK pathways. Thus, D-Trp is a promising therapeutic for diabetic wounds. |
| title | D-Tryptophan Promotes Skin Wound Healing via Extracellular Matrix Remodeling in Normal and Diabetic Models. |
| topic | Animals Wound Healing Diabetes Mellitus, Experimental Mice Extracellular Matrix Tryptophan Male Hypoxia-Inducible Factor 1, alpha Subunit Skin Mice, Inbred C57BL Disease Models, Animal Apoptosis Vascular Endothelial Growth Factor A |
| url | https://pubmed.ncbi.nlm.nih.gov/40806291/ |