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  Knockdown and knockout of beta 1-integrin in hepatocytes impairs liver regeneration through inhibition of growth factor signalling

Speicher, T., Siegenthaler, B., Bogorad, R. L., Ruppert, R., Petzold, T., Padrissa-Altes, S., et al. (2014). Knockdown and knockout of beta 1-integrin in hepatocytes impairs liver regeneration through inhibition of growth factor signalling. NATURE COMMUNICATIONS, 5: 3862. doi:10.1038/ncomms4862.

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 Creators:
Speicher, Tobias1, Author
Siegenthaler, Beat1, Author
Bogorad, Roman L.1, Author
Ruppert, Raphael2, Author              
Petzold, Tobias2, Author              
Padrissa-Altes, Susagna1, Author
Bachofner, Marc1, Author
Anderson, Daniel G.1, Author
Koteliansky, Victor1, Author
Fässler, Reinhard2, Author              
Werner, Sabine1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: IN-VIVO; RNA INTERFERENCE; FACTOR RECEPTOR; EGF RECEPTOR; INTEGRINS; MICE; SIRNA; EFFICIENT; DELIVERY; RAT
 Abstract: The liver has a unique regenerative capability, which involves extensive remodelling of cell-cell and cell-matrix contacts. Here we study the role of integrins in mouse liver regeneration using Cre/loxP-mediated gene deletion or intravenous delivery of beta 1-integrin siRNA formulated into nanoparticles that predominantly target hepatocytes. We show that although short-term loss of beta 1-integrin has no obvious consequences for normal livers, partial hepatectomy leads to severe liver necrosis and reduced hepatocyte proliferation. Mechanistically, loss of beta 1-integrin in hepatocytes impairs ligand-induced phosphorylation of the epidermal growth factor and hepatocyte growth factor receptors, thereby attenuating downstream receptor signalling in vitro and in vivo. These results identify a crucial role and novel mechanism of action of beta 1-integrins in liver regeneration and demonstrate that protein depletion by nanoparticle-based delivery of specific siRNA is a powerful strategy to study gene function in the regenerating liver.

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Language(s): eng - English
 Dates: 2014-05
 Publication Status: Published online
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000337503800006
DOI: 10.1038/ncomms4862
 Degree: -

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Title: NATURE COMMUNICATIONS
Source Genre: Journal
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Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 5 Sequence Number: 3862 Start / End Page: - Identifier: ISSN: 2041-1723