2. Academic Validation
  3. A frog peptide provides new strategies for the intervention against skin wound healing

A frog peptide provides new strategies for the intervention against skin wound healing

  • Cell Mol Biol Lett. 2023 Jul 28;28(1):61. doi: 10.1186/s11658-023-00468-3.
Chao Li # 1,  Zhe Fu # 2,  Tao Jin # 3,  Yixiang Liu 4,  Naixin Liu 2,  Saige Yin 2,  Zhuo Wang 1,  Yubing Huang 1,  Yinglei Wang 2,  Yingxuan Zhang 2,  Jiayi Li 2,  Yutong Wu 2,  Li He 5,  Jing Tang 6,  Ying Wang 7,  Xinwang Yang 8
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, Yunnan, China.
  • 2 Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, Yunnan, China.
  • 3 Department of Orthopedics, 920th Hospital of Joint Logistics Support Force of PLA, Kunming, 650032, Yunnan, China.
  • 4 Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, 650504, Yunnan, China.
  • 5 Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. [email protected].
  • 6 Department of Biochemistry and Molecular Biology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, Yunnan, China. [email protected].
  • 7 Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, 650504, Yunnan, China. [email protected].
  • 8 Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, Yunnan, China. [email protected].
  • # Contributed equally.
PMID: 37501100 DOI: 10.1186/s11658-023-00468-3
Abstract

Background: Amphibian derived pro-healing Peptides as molecular probes might provide a promising strategy for development of drug candidates and elucidation of cellular and molecular mechanisms of skin wound healing. A novel skin amphibian peptide, OA-RD17, was tested for modulation of cellular and molecular mechanisms associated with skin wound healing.

Methods: Cell scratch, cell proliferation, trans-well, and colony formation assays were used to explore the pro-healing ability of peptide OA-RD17 and microRNA-632 (miR-632). Then, the therapeutic effects of OA-RD17 and miR-632 were assessed in mice, diabetic patient ex vivo skin wounds and SD rats. Moreover, hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence staining were performed to detect skin wound tissue regeneration, inflammatory factors expression, and macrophage polarization. Finally, RNA sequencing, molecular docking, co-localization, dual luciferase reporter, real-time quantitative Reverse transcription PCR (RT-qPCR), and Western blotting were used to explore the mechanism of OA-RD17 and miR-632 on facilitating skin wound healing.

Results: The non-toxic peptide (OA-RD17) promoted macrophage proliferation and migration by activating MAPK and suppressed inflammation by inhibiting NF-κB. In keratinocytes, OA-RD17 inhibited excessive inflammation, and activated MAPK via the Toll-like Receptor 4 (TLR4) to promote proliferation and migration, as well as up-regulate the expression of miR-632, which targeted GSK3β to activate Wnt/β-catenin to boost proliferation and migration in a positive feedback manner. Notably, OA-RD17 promoted transition from the inflammatory to proliferative stage, accelerated epidermal and granulation regeneration, and exhibited therapeutic effects on mouse and diabetic patient ex vivo skin wounds. MiR-632 activated Wnt/β-catenin to promote full-thickness skin wound healing in rats.

Conclusions: OA-RD17 exhibited promising therapeutic effects on mice (full-thickness, deep second-degree burns), and ex vivo skin wounds in diabetic patients by regulating macrophages proliferation, migration, and polarization (MAPK, NF-κB), and keratinocytes proliferation and migration (TLR4/MAPK/miR-632/Wnt/β-catenin molecular axis). Moreover, miR-632 also activated Wnt/β-catenin to promote full-thickness skin wound healing in rats. Notably, our results indicate that OA-RD17 and miR-632 are promising pro-healing drug candidates.

Keywords

Amphibians; Inflammation; Pro-healing peptide; Skin wounds; TLR4/MAPK; miR-632/Wnt/β-catenin.

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