Year: 2013
Type: article
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.
Source: Disease Models & Mechanisms
DOI: 10.1242/dmm.011577
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,750
Funders: University of Pittsburgh, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: Role of Fibroblasts, Myeloid Cells and Matrix in PDAC, G1469273482, COBRE for Skeletal Health and Repair, G2329611598, G2513047960, G3856660962, G4325468103, Targeting Pericytes in Cancer, G475519389, Training Program in Cardiovascular Research, Collagen Gene Structure and Expression, Matrix Microenvironment and Liver Fibrosis, G56615411, G6008258537, Epigenetic Modifications in Renal Fibrogenesis, G632314946, Role of Fibroblasts in Cancer, Training Grant in Cancer Biology, Assembly of Type IV Collagen in Health and Disease
OpenAlex ID: W2169092190