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成纤维细胞生长因子作为组织修复和再生疗法

Fibroblast growth factors as tissue repair and regeneration therapeutics.

作者信息

Nunes Quentin M, Li Yong, Sun Changye, Kinnunen Tarja K, Fernig David G

机构信息

Department of Molecular and Clinical Cancer Medicine, NIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom.

Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.

出版信息

PeerJ. 2016 Jan 12;4:e1535. doi: 10.7717/peerj.1535. eCollection 2016.

Abstract

Cell communication is central to the integration of cell function required for the development and homeostasis of multicellular animals. Proteins are an important currency of cell communication, acting locally (auto-, juxta-, or paracrine) or systemically (endocrine). The fibroblast growth factor (FGF) family contributes to the regulation of virtually all aspects of development and organogenesis, and after birth to tissue maintenance, as well as particular aspects of organism physiology. In the West, oncology has been the focus of translation of FGF research, whereas in China and to an extent Japan a major focus has been to use FGFs in repair and regeneration settings. These differences have their roots in research history and aims. The Chinese drive into biotechnology and the delivery of engineered clinical grade FGFs by a major Chinese research group were important enablers in this respect. The Chinese language clinical literature is not widely accessible. To put this into context, we provide the essential molecular and functional background to the FGF communication system covering FGF ligands, the heparan sulfate and Klotho co-receptors and FGF receptor (FGFR) tyrosine kinases. We then summarise a selection of clinical reports that demonstrate the efficacy of engineered recombinant FGF ligands in treating a wide range of conditions that require tissue repair/regeneration. Alongside, the functional reasons why application of exogenous FGF ligands does not lead to cancers are described. Together, this highlights that the FGF ligands represent a major opportunity for clinical translation that has been largely overlooked in the West.

摘要

细胞通讯是多细胞动物发育和体内平衡所需细胞功能整合的核心。蛋白质是细胞通讯的重要介质,可在局部(自分泌、旁分泌或近分泌)或全身(内分泌)发挥作用。成纤维细胞生长因子(FGF)家族几乎参与了发育和器官形成各个方面的调节,出生后还参与组织维持以及机体生理的特定方面。在西方,肿瘤学一直是FGF研究转化的重点,而在中国以及在一定程度上在日本,主要重点是在修复和再生领域应用FGF。这些差异源于研究历史和目标。中国在生物技术方面的发展以及一个主要的中国研究团队提供工程化临床级FGF,在这方面起到了重要推动作用。中文临床文献的获取并不广泛。为了说明这一点,我们提供了FGF通讯系统的基本分子和功能背景,涵盖FGF配体、硫酸乙酰肝素和Klotho共受体以及FGF受体(FGFR)酪氨酸激酶。然后我们总结了一系列临床报告,这些报告证明了工程化重组FGF配体在治疗各种需要组织修复/再生的病症方面的疗效。同时,还描述了应用外源性FGF配体不会导致癌症的功能原因。总之,这突出表明FGF配体代表了临床转化的一个主要机会,而这在西方很大程度上被忽视了。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bc3/4715458/0823b7a8dffa/peerj-04-1535-g001.jpg

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