title: Type XVIII collagen is essential for survival during acute liver injury in mice.
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.
authors.affiliation: Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Duncan
authors.forename: Changqing
authors.initials: C
authors.lastname: Yang
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Tanjore
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Boyle
authors.forename: Doruk
authors.initials: D
authors.lastname: Keskin
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Michael
authors.initials: M
authors.lastname: Zeisberg
authors.forename: Bjorn R
authors.initials: BR
authors.lastname: Olsen
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D016923:Cell Death; D043170:Collagen Type XVIII / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D039222:Integrin alpha1beta1 / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D011485:Protein Binding; D015398:Signal Transduction; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D043170:Collagen Type XVIII; D039222:Integrin alpha1beta1; D016212:Transforming Growth Factor beta; D002251:Carbon Tetrachloride