Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis
- Burns & Trauma Vol. 10, Issue 1, (2022)
- 作者机构：
1. Department of Anatomy and Histology & Embryology
2. Kunming Medical University
3. Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes
4. Yunnan MinZu University
5. Institutional Center for Shared Technologies and Facilities of Kunming Institute of Zoology, Chinese Academy of Sciences
6. Endocrinology Department of Affiliated Hospital of Yunnan University
7. Department of Dermatology, First Affiliated Hospital of Kunming Medical University
- 作者简介：
- 基金信息：
DOI：10.1093/burnst/tkac032
CLC：Published：2022，
Published Online：12 July 2022，
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Yue Zhang, Ying Wang, Lin Zeng, Yixiang Liu, Huiling Sun, Shanshan Li, Siyu Wang, Longjun Shu, Naixin Liu, Saige Yin, Junsong Wang, Dan Ni, Yutong Wu, Ying Yang, Li He, Buliang Meng, Xinwang Yang, Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis, Burns & Trauma, Volume 10, 2022, tkac032, https://doi.org/10.1093/burnst/tkac032
Yue Zhang, Ying Wang, Lin Zeng, Yixiang Liu, Huiling Sun, Shanshan Li, Siyu Wang, Longjun Shu, Naixin Liu, Saige Yin, Junsong Wang, Dan Ni, Yutong Wu, Ying Yang, Li He, Buliang Meng, Xinwang Yang, Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis, Burns & Trauma, Volume 10, 2022, tkac032, https://doi.org/10.1093/burnst/tkac032 DOI：
摘要
Abstract
BackgroundAmphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds. MicroRNAs (miRNAs) are also considered promising targets for the development of effective therapies against skin wounds. However
further research in this field is anticipated. This study aims to identify and provide a new peptide drug candidate
as well as to explore the underlying miRNA mechanisms and possible miRNA drug target for skin wound healing.MethodsA combination of Edman degradation
mass spectrometry and cDNA cloning were adopted to determine the amino acid sequence of a peptide that was fractionated from the secretion of Odorrana andersonii frog skin using gel-filtration and reversed-phase high-performance liquid chromatography. The toxicity of the peptide was evaluated by Calcein-AM/propidium iodide (PI) double staining against human keratinocytes (HaCaT cells)
hemolytic activity against mice blood cells and acute toxicity against mice. The stability of the peptide in plasma was also evaluated. The prohealing potency of the peptide was determined by MTS
scratch healing and a Transwell experiment against HaCaT cells
full-thickness injury wounds and scald wounds in the dorsal skin of mice. miRNA transcriptome sequencing analysis
enzyme-linked immunosorbent assay
real-time polymerase chain reaction and western blotting were performed to explore the molecular mechanisms.ResultsA novel peptide homodimer (named OA-GL17d) that contains a disulfide bond between the 16th cysteine residue of the peptide monomer and the sequence ‘GLFKWHPRCGEEQSMWT’ was identified. Analysis showed that OA-GL17d exhibited no hemolytic activity or acute toxicity
but effectively promoted keratinocyte proliferation and migration and strongly stimulated the repair of full-thickness injury wounds and scald wounds in the dorsal skin of mice. Mechanistically
OA-GL17d decreased the level of miR-663a to increase the level of transforming growth factor-β1 (TGF-β1) and activate the subsequent TGF-β1/Smad signaling pathway
thereby resulting in accelerated skin wound re-epithelialization and granular tissue formation.ConclusionsOur results suggest that OA-GL17d is a new peptide drug candidate for skin wound repair. This study emphasizes the importance of exogenous peptides as molecular probes for exploring competing endogenous RNA mechanisms and indicates that miR-663a may be an effective target for promoting skin repair.
关键词
Keywords
microRNAmiR-663aWound healingPeptideAmphibianHuman keratinocytesOA-G17dChronic woundskinTransforming growth factor-β1Smad
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