D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes
Abstract Background Diabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related d...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01070-3 |
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| author | Jialiang Luo Tianxing Wu Jing Zhang Zhicheng Liang Weijie Shao Di Wang Lei Li Daming Zuo Jia Zhou |
| author_facet | Jialiang Luo Tianxing Wu Jing Zhang Zhicheng Liang Weijie Shao Di Wang Lei Li Daming Zuo Jia Zhou |
| author_sort | Jialiang Luo |
| collection | DOAJ |
| description | Abstract Background Diabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related disorders. Methods Here, we examined the potential effect of D-mannose during wound healing process in streptozotocin (STZ)-induced diabetes mice in vivo and by culturing keratinocytes under high glucose condition in vitro. The skin lesion healing was recorded in photos and evaluated by histochemical staining. What’s more, the advanced glycation end products (AGEs) concentration in blood and mice skin was quantified. Apoptotic cells were assessed by flow cytometry and Western blotting. Inflammatory cytokines and cellular differential gene expression levels were measured by real-time PCR. The expression of the AMPK/Nrf2/HO-1 signaling-related molecules was determined by Western blotting. Results We first found that topical supplementation of D-mannose remarkably improved skin wound healing in diabetes mice. Furthermore, both in vivo and in vitro experiments demonstrated that D-mannose reduced the AGEs generation. Mechanistically, D-mannose inhibited AGEs, then upregulated AMPK/Nrf2/HO-1 signaling in the context of high glucose to maintain keratinocyte normal functions, which positively influenced macrophage and fibroblast to accelerate diabetic wound healing. Noteworthily, these protective effects of D-mannose were abolished by the pretreatment with inhibitors of AGEs or AMPK. Conclusion As far as we know, this is the first study exploring the protective role of D-mannose on diabetic wound healing via topical supplementation. We find that D-mannose protects keratinocytes from high glucose stimulation via inhibition of AGEs formation as well as orchestrates inflammatory microenvironment in diabetic wounded skin, suggesting its supplementation as a potential therapy to promote refractory wound healing in diabetic patients. |
| format | Article |
| id | doaj-art-3047956377444336958e948a1b208dfe |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-3047956377444336958e948a1b208dfe2025-01-19T12:27:24ZengBMCMolecular Medicine1528-36582025-01-0131111410.1186/s10020-025-01070-3D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytesJialiang Luo0Tianxing Wu1Jing Zhang2Zhicheng Liang3Weijie Shao4Di Wang5Lei Li6Daming Zuo7Jia Zhou8Institute of Molecular Immunology, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangdong Province Key Laboratory of Immune Regulation and Immunotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical UniversityThe Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Immunology, School of Basic Medical Sciences, Southern Medical UniversityDepartment of Immunology, School of Basic Medical Sciences, Southern Medical UniversityDepartment of Immunology, School of Basic Medical Sciences, Southern Medical UniversityDepartment of Dermatology, Dermatology Hospital of Southern Medical University, Southern Medical UniversityInstitute of Molecular Immunology, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangdong Province Key Laboratory of Immune Regulation and Immunotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical UniversityInstitute of Molecular Immunology, Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangdong Province Key Laboratory of Immune Regulation and Immunotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical UniversityDepartment of Immunology, School of Basic Medical Sciences, Southern Medical UniversityAbstract Background Diabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related disorders. Methods Here, we examined the potential effect of D-mannose during wound healing process in streptozotocin (STZ)-induced diabetes mice in vivo and by culturing keratinocytes under high glucose condition in vitro. The skin lesion healing was recorded in photos and evaluated by histochemical staining. What’s more, the advanced glycation end products (AGEs) concentration in blood and mice skin was quantified. Apoptotic cells were assessed by flow cytometry and Western blotting. Inflammatory cytokines and cellular differential gene expression levels were measured by real-time PCR. The expression of the AMPK/Nrf2/HO-1 signaling-related molecules was determined by Western blotting. Results We first found that topical supplementation of D-mannose remarkably improved skin wound healing in diabetes mice. Furthermore, both in vivo and in vitro experiments demonstrated that D-mannose reduced the AGEs generation. Mechanistically, D-mannose inhibited AGEs, then upregulated AMPK/Nrf2/HO-1 signaling in the context of high glucose to maintain keratinocyte normal functions, which positively influenced macrophage and fibroblast to accelerate diabetic wound healing. Noteworthily, these protective effects of D-mannose were abolished by the pretreatment with inhibitors of AGEs or AMPK. Conclusion As far as we know, this is the first study exploring the protective role of D-mannose on diabetic wound healing via topical supplementation. We find that D-mannose protects keratinocytes from high glucose stimulation via inhibition of AGEs formation as well as orchestrates inflammatory microenvironment in diabetic wounded skin, suggesting its supplementation as a potential therapy to promote refractory wound healing in diabetic patients.https://doi.org/10.1186/s10020-025-01070-3D-mannoseDiabetic wound healingAGEs formationKeratinocytesAMPK/Nrf2/HO-1 signaling |
| spellingShingle | Jialiang Luo Tianxing Wu Jing Zhang Zhicheng Liang Weijie Shao Di Wang Lei Li Daming Zuo Jia Zhou D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes Molecular Medicine D-mannose Diabetic wound healing AGEs formation Keratinocytes AMPK/Nrf2/HO-1 signaling |
| title | D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes |
| title_full | D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes |
| title_fullStr | D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes |
| title_full_unstemmed | D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes |
| title_short | D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes |
| title_sort | d mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes |
| topic | D-mannose Diabetic wound healing AGEs formation Keratinocytes AMPK/Nrf2/HO-1 signaling |
| url | https://doi.org/10.1186/s10020-025-01070-3 |
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