caa a22 4500 475774647 CHVBK 20180406123627.0 cr unu---uuuuu 170329e20000601xx s 000 0 eng 10.1007/s004180000150 doi (NATIONALLICENCE)springer-10.1007/s004180000150 Expression of matrix metalloproteinases and their inhibitors during hepatic tissue repair in the rat [Elektronische Daten] [Thomas Knittel, Mirko Mehde, Anka Grundmann, Bernhard Saile, Jens-Gerd Scharf, Giuliano Ramadori] Abstract.: Matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) are thought to play an essential role in liver injury associated with tissue remodeling. However, their distinct expression profile in different liver repair models still remains to be established. Hepatic expression of collagenase (MMP-13), gelatinasesA and B (MMP-2, -9), stromelysin-1 and -2 (MMP-3, -10), membrane-type MMP-1 (MMP-14), and TIMP-1 and -2 was studied following single and repeated CCl4-mediated injury and after partial hepatectomy. Expression was analyzed by reverse transcription-PCR (RT-PCR), northern blot analysis, zymography, and immunohistochemistry. Following a single toxic liver injury, MMPs and TIMPs were induced in a distinct time frame in that expression of most MMPs was induced during the early phase of liver injury, was maximal during the inflammatory reaction, and was diminished in the recovery phase. In contrast, TIMP and MMP-2 steady state mRNA levels remained constant in the early phase, were strongly induced during tissue inflammation, and remained increased until the recovery phase. Interestingly, hepatic TNF-α expression paralleled the MMP induction profile, while the increase of TGF-β1 expression mapped to the increase of TIMPs. Chronic liver injury was accompanied by an increase in the steady state mRNA levels of MMP-2 and TIMPs, while other MMPs remained more or less unchanged or were diminished. Partial hepatectomy was followed by a dramatic increase of MMP-14 and to a lesser extent also of TIMP-1 expression; other MMPs and TIMPs were not significantly induced. Liver injury is accompanied by profound changes in hepatic MMP/TIMP expression, the latter being critically dependent on the type of injury. Single toxic injury resulting in complete restoration was characterized by a sequential induction of MMPs and TIMPs suggesting initial matrix breakdown and matrix restoration thereafter. Chronic liver injury leading to fibrosis displays overall diminished matrix degradation mainly through TIMP induction, while liver regeneration induced by partial hepatectomy caused an induction of MMP-14 and TIMP-1 only, which might be unrelated to matrix turnover but connected to pericellular fibrinolysis or fibrolysis required for hepatocellular replication. Springer-Verlag, 2000 MMP TIMP Fibrosis Inflammation Regeneration Liver nationallicence Knittel Thomas Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut Mehde Mirko Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut Grundmann Anka Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut Saile Bernhard Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut Scharf Jens-Gerd Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut Ramadori Giuliano Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut https://doi.org/10.1007/s004180000150 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004180000150 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Knittel Thomas Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut NATIONALLICENCE 700 1- Mehde Mirko Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut NATIONALLICENCE 700 1- Grundmann Anka Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut NATIONALLICENCE 700 1- Saile Bernhard Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut NATIONALLICENCE 700 1- Scharf Jens-Gerd Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut NATIONALLICENCE 700 1- Ramadori Giuliano Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Robert Koch Strasse 40, 37075 Göttingen, Germany aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer