Liver fibrosis and regeneration in dogs and cats : An immunohistochemical approach

Abstract

Canine and feline liver disease is a common phenomenon with usually an unfavourable outcome. Improved insight in the species-specific reaction of dogs and cats is needed to facilitate development of new therapeutic strategies. First, the complex process of liver tissue repair is discussed in three parts: 1) major signalling pathways are described, 2) followed by the relevant cell types and 3) an integrated outline of events is presented. Finally, the insights of the PhD thesis “Liver fibrosis and regeneration in dogs and cats: An immunohistochemical approach” are discussed. This study contains the first identification of a liver progenitor cell compartment in the dog and cat, comparable to human liver. Several key cell types regarding hepatic fibrosis and regeneration were identified immunohistochemically: hepatocytes, cholangiocytes, fibroblasts including hepatic stellate cells and progenitor cells. Also, localization of major signaling factors in spontaneous canine hepatitis are investigated: hepatocyte growth factor (HGF), HGF receptor (c-Met) and TGF-beta-receptor1 (TGF-β-R1), and compared to associated messenger-RNA and protein expression levels. Remarkably, the absolute HGF availability does not seem the limiting factor in hepatic regeneration. Tenascin-C staining combined with α-smooth muscle actin staining could be useful to assess the type or activity of the fibrosing process, and HSC activation, respectively. This implies enhanced turnover of extracellular matrix, and a poorer prognosis, but also potential reversibility of fibrosis. Thus such an indication of fibrosis activity may predict potential therapeutically accessibility and success rate. Optimal use of liver biopsies and minimal burdening of the animal patient proved to be reached by taking at least two biopsies: one for histology and one for molecular assays. This work supports the idea that in hepatology, spontaneous hepatologic canine patients may have large potential to bridge the existing gap between rodent animal models and bedside medicine in man.