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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。

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

作者信息

Farooq Mariya, Hwang Moonjung, Khan Abdul Waheed, Batool Maria, Ahmad Bilal, Kim Wook, Kim Moon Suk, Choi Sangdun

机构信息

S&K Therapeutics, Ajou University Campus Plaza 418, Worldcup-ro 199, Yeongton-gu, Suwon 16502, Republic of Korea; Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.

Department of Molecular Science and Technology, Ajou University, Suwon 16499, Republic of Korea.

出版信息

Life Sci. 2025 Mar 1;364:123432. doi: 10.1016/j.lfs.2025.123432. Epub 2025 Jan 28.

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.

摘要

目的

成纤维细胞生长因子(FGF)是一类通过FGF受体(FGFR)发挥作用的分泌性化学物质。本研究旨在探讨一种新型肽FAP1(FGFR激动肽1)在组织再生和修复中的作用。研究其是否能模拟碱性成纤维细胞生长因子(bFGF),并在体外和体内加速伤口愈合。

主要方法

在本研究中,设计了一种新型肽,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(MAPK)激活)的影响。通过表面等离子体共振(SPR)分析和与FGFR抑制剂厄达替尼联合处理来确认特异性。在体内,在小鼠模型中测试FAP1对糖尿病伤口愈合的影响,检测胶原蛋白生成以及角质形成细胞和成纤维细胞的迁移和增殖情况。

主要发现

FAP1能特异性地使FGFR磷酸化并激活MAPK,类似于bFGF。在体外,它能诱导细胞增殖并加速伤口愈合。在体内,FAP1通过增加胶原蛋白生成、促进角质形成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确认了FAP1的特异性。

意义

FAP1显示出作为天然bFGF用于皮肤组织再生和修复的新型药理学替代物的潜力。其加速伤口愈合的能力及其对FGFR的特异性表明,FAP1在治疗应用中可作为bFGF蛋白的一种经济有效的替代品。

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