The regenerative response to drug and toxin induced liver injury induces changes to the hepatic stroma, including the extracellular matrix. While the extracellular matrix is known to undergo significant 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 the α1β1 integrin, integrin linked kinase, and 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 crucial for hepatocyte survival during injury and stress.
- Received December 18, 2012.
- Accepted March 29, 2013.
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