Spatiotemporal Characterization of the Cellular and Molecular Contributors to Liver Fibrosis in a Murine Hepatotoxic-Injury Model
Michelle Melino, Victoria L Gadd, Kylie A Alexander, Lynette Beattie, Katie E Lineburg, Michelle Martinez, Bianca Teal, Laetitia Le Texier, Katharine M Irvine, Gregory C Miller, Glen M Boyle, Geoffrey R Hill, Andrew D Clouston, Elizabeth E Powel, Kelli PA MacDonald
The American Journal of Pathology | ELSEVIER SCIENCE INC | Published : 2016
The interplay between the inflammatory infiltrate and tissue resident cell populations invokes fibrogenesis. However, the temporal and mechanistic contributions of these cells to fibrosis are obscure. To address this issue, liver inflammation, ductular reaction (DR), and fibrosis were induced in C57BL/6 mice by thioacetamide administration for up to 12 weeks. Thioacetamide treatment induced two phases of liver fibrosis. A rapid pericentral inflammatory infiltrate enriched in F4/80(+) monocytes co-localized with SMA(+) myofibroblasts resulted in early collagen deposition, marking the start of an initial fibrotic phase (1 to 6 weeks). An expansion of bone marrow-derived macrophages preceded a ..View full abstract
Awarded by National Health and Medical Research Council of Australia
Supported by the National Health and Medical Research Council of Australia (APP1044650). K.P.A.M. is a Cancer Council QLD Senior Research Fellow, E.E.P. is an NHMRC Practitioner Fellow, and K.M.I. is an Australian Liver Foundation Fellow.