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肝细胞生长因子/分散因子kringle 1 结构域的二聚化提供了一种有效的 MET 受体激动剂。

Dimerization of kringle 1 domain from hepatocyte growth factor/scatter factor provides a potent MET receptor agonist.

机构信息

Department of Molecular Medicine, University of Pavia, Unit of Immunology and General Pathology Section, Pavia, Italy.

University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019, UMR 9017, CIIL, Center for Infection and Immunity of Lille, Lille, France.

出版信息

Life Sci Alliance. 2022 Jul 29;5(12):e202201424. doi: 10.26508/lsa.202201424.

DOI:10.26508/lsa.202201424
PMID:35905995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9348577/
Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) and its cognate receptor MET play several essential roles in embryogenesis and regeneration in postnatal life of epithelial organs such as the liver, kidney, lung, and pancreas, prompting a strong interest in harnessing HGF/SF-MET signalling for regeneration of epithelial organs after acute or chronic damage. The limited stability and tissue diffusion of native HGF/SF, however, which reflect the tightly controlled, local mechanism of action of the morphogen, have led to a major search of HGF/SF mimics for therapy. In this work, we describe the rational design, production, and characterization of K1K1, a novel minimal MET agonist consisting of two copies of the kringle 1 domain of HGF/SF in tandem orientation. K1K1 is highly stable and displays biological activities equivalent or superior to native HGF/SF in a variety of in vitro assay systems and in a mouse model of liver disease. These data suggest that this engineered ligand may find wide applications in acute and chronic diseases of the liver and other epithelial organs dependent of MET activation.

摘要

肝细胞生长因子/分散因子（HGF/SF）及其同源受体 MET 在胚胎发生和出生后上皮器官（如肝脏、肾脏、肺和胰腺）的再生中发挥着重要作用，这促使人们强烈关注利用 HGF/SF-MET 信号通路来实现上皮器官在急性或慢性损伤后的再生。然而，天然 HGF/SF 的有限稳定性和组织扩散性反映了形态发生素的严格控制的局部作用机制，这导致了对 HGF/SF 模拟物的广泛研究。在这项工作中，我们描述了 K1K1 的合理设计、生产和表征，K1K1 是一种新型的最小 MET 激动剂，由 HGF/SF 的两个串联kringle 1 结构域组成。K1K1 高度稳定，并在各种体外测定系统和小鼠肝脏疾病模型中显示出与天然 HGF/SF 相当或更优的生物学活性。这些数据表明，这种工程化配体可能在依赖 MET 激活的急性和慢性肝脏及其他上皮器官疾病中具有广泛的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/0630e9976e1a/LSA-2022-01424_FigS8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/9bc4dd18588c/LSA-2022-01424_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/87de312abb53/LSA-2022-01424_Fig2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/c1b3aca6179f/LSA-2022-01424_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/2bdf11d2a898/LSA-2022-01424_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/d14e45919156/LSA-2022-01424_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/d8e0f7879e2a/LSA-2022-01424_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/061b4514b8f1/LSA-2022-01424_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/a5a92bd3e95f/LSA-2022-01424_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/e7b21f5c4155/LSA-2022-01424_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/a77b5b053244/LSA-2022-01424_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/2eefa81c6a6b/LSA-2022-01424_FigS6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/2a5206049faf/LSA-2022-01424_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/8303391548cd/LSA-2022-01424_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/15aaccfde8de/LSA-2022-01424_FigS7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/0630e9976e1a/LSA-2022-01424_FigS8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/9bc4dd18588c/LSA-2022-01424_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/87de312abb53/LSA-2022-01424_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/2e1d488346ed/LSA-2022-01424_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/c1b3aca6179f/LSA-2022-01424_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/2bdf11d2a898/LSA-2022-01424_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/d14e45919156/LSA-2022-01424_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/d8e0f7879e2a/LSA-2022-01424_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/061b4514b8f1/LSA-2022-01424_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/a5a92bd3e95f/LSA-2022-01424_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/e7b21f5c4155/LSA-2022-01424_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/a77b5b053244/LSA-2022-01424_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/2eefa81c6a6b/LSA-2022-01424_FigS6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/2a5206049faf/LSA-2022-01424_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/8303391548cd/LSA-2022-01424_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/15aaccfde8de/LSA-2022-01424_FigS7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f39/9348577/0630e9976e1a/LSA-2022-01424_FigS8.jpg

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J Clin Transl Hepatol. 2021 Feb 28;9(1):40-50. doi: 10.14218/JCTH.2020.00055. Epub 2020 Dec 9.
3
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