Type XVIII collagen is essential for survival during acute liver injury in mice

Michael B. Duncan, Changqing Yang, Harikrishna Tanjore, Patrick M. Boyle, Doruk Keskin, Hikaru Sugimoto, Michael Zeisberg, Bjorn R. Olsen, Raghu Kalluri

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The regenerative response to drug- and toxin-induced liver injury induces changes to the hepatic stroma, including the extracellular matrix. Although the extracellular matrix is known to undergo changes during the injury response, its impact on maintaining hepatocyte function and viability in this process remains largely unknown. We demonstrate that recovery from toxin-mediated injury is impaired in mice deficient in a key liver extracellular matrix molecule, type XVIII collagen, and results in rapid death. The type-XVIII-collagen-dependent response to liver injury is mediated by survival signals induced by α1β1 integrin, integrin linked kinase and the Akt pathway, and mice deficient in either α1β1 integrin or hepatocyte integrin linked kinase also succumb to toxic liver injury. These findings demonstrate that type XVIII collagen is an important functional component of the liver matrix microenvironment and is crucial for hepatocyte survival during injury and stress.

Original languageEnglish (US)
Pages (from-to)942-951
Number of pages10
JournalDMM Disease Models and Mechanisms
Volume6
Issue number4
DOIs
Publication statusPublished - Jul 1 2013

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ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Duncan, M. B., Yang, C., Tanjore, H., Boyle, P. M., Keskin, D., Sugimoto, H., ... Kalluri, R. (2013). Type XVIII collagen is essential for survival during acute liver injury in mice. DMM Disease Models and Mechanisms, 6(4), 942-951. https://doi.org/10.1242/dmm.011577