Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis

作者：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 · 发表于：Burns & Trauma · 年份：2022 · DOI：10.1093/burnst/tkac032 · 被引用次数：45 · 研究领域：Wound Healing and Treatments、Antimicrobial Peptides and Activities、Histone Deacetylase Inhibitors Research

Background: Amphibian-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. Methods: 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. Results: A 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 sh...