%0 Journal Article
%T Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model
%A Sanne Skovg£¿rd Veidal
%A Mette Juul Nielsen
%A Diana Julie Leeming
%A Morten Asser Karsdal
%J BMC Research Notes
%D 2012
%I BioMed Central
%R 10.1186/1756-0500-5-686
%X In vivo: Rats were treated for 8£¿weeks with CCl4/Intralipid. Liver slices were cultured for 48£¿hours. Levels of C3M were determined in the supernatants of slices cultured without treatment, treated with GM6001 (positive control) or treated with IBMX (phosphodiesterase inhibitor). Enzymatic activity of MMP-2 and MMP-9 were studied by gelatin zymography. Ex vivo: The levels of serum C3M increased 77% in the CCl4-treated rats at week 8 (p£¿<£¿0.01); Levels of C3M increased significantly by 100% in fibrotic liver slices compared to controls after 48£¿hrs (p£¿<£¿0.01). By adding GM6001 or IBMX to the media, C3M was restored to control levels. Gelatin zymography demonstrated CCl4-treated animals had highly increased MMP-9, but not MMP-2 activity, compared to slices derived from control animals.We have combined an ex vivo model of liver fibrosis with measurement of a biochemical marker of collagen degradation in the condition medium. This technology may be used to evaluate the molecular process leading to structural fibrotic changes, as collagen species are the predominant structural part of fibrosis. These data suggest that modulation of cAMP may play a role in regulation of collagen degradation associated with liver fibrosis.Liver fibrosis due to viral or alcohol-induced injury is one of the leading causes of death worldwide [1]. Liver biopsy is the most commonly used method for fibrosis assessment, but it is invasive, associated with patient discomfort and, in rare cases, with serious complications [2-4]. Therefore, research has focused on the evaluation of non-invasive methods for the assessment of liver fibrosis [5], including a highly enforced effort in discovering and developing biochemical markers for liver fibrosis assessment. In alignment there is an urgent need for applied translational science, in which information from preclinical settings may be translated to clinical settings. One such approach may be to investigate the same biochemical analyte in liver explants
%K Precision-cut liver slices
%K Fibrosis
%K Ex vivo
%K cAMP
%U http://www.biomedcentral.com/1756-0500/5/686