PMID- 35905995
OWN - NLM
STAT- MEDLINE
DCOM- 20220802
LR  - 20221121
IS  - 2575-1077 (Electronic)
IS  - 2575-1077 (Linking)
VI  - 5
IP  - 12
DP  - 2022 Jul 29
TI  - Dimerization of kringle 1 domain from hepatocyte growth factor/scatter factor 
      provides a potent MET receptor agonist.
LID - 10.26508/lsa.202201424 [doi]
LID - e202201424
AB  - 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.
CI  - (c) 2022 de Nola et al.
FAU - de Nola, Giovanni
AU  - de Nola G
AD  - Department of Molecular Medicine, University of Pavia, Unit of Immunology and 
      General Pathology Section, Pavia, Italy.
FAU - Leclercq, Berenice
AU  - Leclercq B
AD  - University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019, 
      UMR 9017, CIIL, Center for Infection and Immunity of Lille, Lille, France.
FAU - Mougel, Alexandra
AU  - Mougel A
AD  - University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019, 
      UMR 9017, CIIL, Center for Infection and Immunity of Lille, Lille, France.
FAU - Taront, Solenne
AU  - Taront S
AUID- ORCID: 0000-0001-5850-7291
AD  - University of Lille, Inserm, CHU Lille, U1286, INFINITE, Institute for 
      Translational Research in Inflammation, Lille, France.
FAU - Simonneau, Claire
AU  - Simonneau C
AD  - Roche Pharmaceutical Research and Early Development (pRED), Pharmaceutical 
      Sciences, Roche Innovation Center Basel, Basel, Switzerland.
FAU - Forneris, Federico
AU  - Forneris F
AUID- ORCID: 0000-0002-7818-1804
AD  - The Armenise-Harvard Laboratory of Structural Biology, Department of Biology and 
      Biotechnology, University of Pavia, Pavia, Italy.
FAU - Adriaenssens, Eric
AU  - Adriaenssens E
AD  - University of Lille, CNRS, INSERM, CHU Lille, Centre Oscar Lambret, UMR 9020, UMR 
      1277, Canther, Cancer Heterogeneity, Plasticity and Resistance to Therapies, 
      Lille, France.
FAU - Drobecq, Herve
AU  - Drobecq H
AD  - University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019, 
      UMR 9017, CIIL, Center for Infection and Immunity of Lille, Lille, France.
FAU - Iamele, Luisa
AU  - Iamele L
AD  - Department of Molecular Medicine, University of Pavia, Unit of Immunology and 
      General Pathology Section, Pavia, Italy.
FAU - Dubuquoy, Laurent
AU  - Dubuquoy L
AUID- ORCID: 0000-0003-3596-5497
AD  - University of Lille, Inserm, CHU Lille, U1286, INFINITE, Institute for 
      Translational Research in Inflammation, Lille, France.
FAU - Melnyk, Oleg
AU  - Melnyk O
AUID- ORCID: 0000-0002-3863-5613
AD  - University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019, 
      UMR 9017, CIIL, Center for Infection and Immunity of Lille, Lille, France.
FAU - Gherardi, Ermanno
AU  - Gherardi E
AUID- ORCID: 0000-0002-0016-2945
AD  - Department of Molecular Medicine, University of Pavia, Unit of Immunology and 
      General Pathology Section, Pavia, Italy.
FAU - de Jonge, Hugo
AU  - de Jonge H
AUID- ORCID: 0000-0003-2777-4084
AD  - Department of Molecular Medicine, University of Pavia, Unit of Immunology and 
      General Pathology Section, Pavia, Italy hugo.dejonge@unipv.it.
FAU - Vicogne, Jerome
AU  - Vicogne J
AUID- ORCID: 0000-0001-8360-7497
AD  - University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019, 
      UMR 9017, CIIL, Center for Infection and Immunity of Lille, Lille, France 
      jerome.vicogne@ibl.cnrs.fr.
LA  - eng
SI  - PDB/3HN4
SI  - PDB/3SP8
SI  - PDB/7OCL
SI  - PDB/7OCM
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220729
PL  - United States
TA  - Life Sci Alliance
JT  - Life science alliance
JID - 101728869
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Dimerization
MH  - *Hepatocyte Growth Factor/metabolism
MH  - *Kringles
MH  - Liver/metabolism
MH  - Mice
MH  - Proto-Oncogene Proteins c-met/agonists/metabolism
PMC - PMC9348577
COIS- The authors declare no competing interests. The Universities of Lille and Pavia 
      have filed a joint patent on K1K1 (patent number WO2016116578A1).
EDAT- 2022/07/30 06:00
MHDA- 2022/08/03 06:00
PMCR- 2022/07/29
CRDT- 2022/07/29 20:33
PHST- 2022/02/25 00:00 [received]
PHST- 2022/07/01 00:00 [revised]
PHST- 2022/07/06 00:00 [accepted]
PHST- 2022/07/29 20:33 [entrez]
PHST- 2022/07/30 06:00 [pubmed]
PHST- 2022/08/03 06:00 [medline]
PHST- 2022/07/29 00:00 [pmc-release]
AID - 5/12/e202201424 [pii]
AID - LSA-2022-01424 [pii]
AID - 10.26508/lsa.202201424 [doi]
PST - epublish
SO  - Life Sci Alliance. 2022 Jul 29;5(12):e202201424. doi: 10.26508/lsa.202201424.