Identification of a novel fibroblast growth factor receptor-agonistic peptide and its effect on diabetic wound healing

IF 5.1 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-03-01 Epub Date: 2025-01-28 DOI:10.1016/j.lfs.2025.123432
Mariya Farooq , Moonjung Hwang , Abdul Waheed Khan , Maria Batool , Bilal Ahmad , Wook Kim , Moon Suk Kim , Sangdun Choi
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Abstract

Aims

Fibroblast growth factor (FGF) is a broad class of secretory chemicals that act via FGF receptors (FGFR). The study aims to explore the role of a novel peptide, FAP1 (FGFR-agonistic peptide 1), in tissue regeneration and repair. It investigates whether FAP1 mimics basic fibroblast growth factor (bFGF) and accelerates wound healing both in vitro and in vivo.

Main methods

In this study, a novel peptide was designed and its ability to mimic bFGF was assessed through different in vitro experiments including its effect on cell proliferation, wound healing, cell signaling including FGFR1 phosphorylation and activation of mitogen-activated protein kinases (MAPKs). Specificity was confirmed through surface plasmon resonance (SPR) analysis and co-treatment with FGFR inhibitor, erdafitinib. In vivo, the effect of FAP1 on diabetic wound healing was tested in a mouse model, examining collagen production and the migration and proliferation of keratinocytes and fibroblasts.

Key findings

FAP1 specifically phosphorylated FGFR and activated MAPKs similar to bFGF. In vitro, it induced cell proliferation and accelerated wound healing. In vivo, FAP1 improved diabetic wound healing by increasing collagen production and promoting keratinocyte and fibroblast migration and proliferation. The specificity of FAP1 was confirmed through SPR.

Significance

FAP1 shows potential as a novel pharmacological alternative to natural bFGF for skin tissue regeneration and repair. Its ability to accelerate wound healing and its specificity for FGFR suggest that FAP1 could serve as a cost-effective substitute for bFGF protein in therapeutic applications.

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一种新型成纤维细胞生长因子受体激动肽的鉴定及其对糖尿病伤口愈合的影响。
目的:成纤维细胞生长因子(FGF)是一类广泛的分泌化学物质,通过FGF受体(FGFR)起作用。该研究旨在探索一种新型肽FAP1 (FGFR-agonistic peptide 1)在组织再生和修复中的作用。在体外和体内研究FAP1是否模拟碱性成纤维细胞生长因子(bFGF)并加速伤口愈合。主要方法:本研究设计了一种新型多肽,并通过不同的体外实验评估其模拟bFGF的能力,包括其对细胞增殖、伤口愈合、细胞信号传导(包括FGFR1磷酸化和丝裂原活化蛋白激酶(MAPKs)的激活)的影响。通过表面等离子体共振(SPR)分析和与FGFR抑制剂厄达非替尼(erdafitinib)共同治疗,证实了特异性。在体内,在小鼠模型中测试了FAP1对糖尿病伤口愈合的影响,检测了胶原蛋白的产生以及角化细胞和成纤维细胞的迁移和增殖。关键发现:FAP1特异性磷酸化FGFR并激活类似bFGF的mapk。在体外,它能诱导细胞增殖,加速伤口愈合。在体内,FAP1通过增加胶原生成、促进角化细胞和成纤维细胞的迁移和增殖来改善糖尿病伤口愈合。通过SPR证实FAP1的特异性。意义:FAP1有潜力作为天然bFGF的一种新的药理替代品,用于皮肤组织再生和修复。其加速伤口愈合的能力和对FGFR的特异性表明,FAP1可以作为bFGF蛋白在治疗应用中具有成本效益的替代品。
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来源期刊
Life sciences
Life sciences 医学-药学
CiteScore
12.20
自引率
1.60%
发文量
841
审稿时长
6 months
期刊介绍: Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
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