Participation of cathepsin L in collagen degradation during the regression of experimental hepatic cirrhosis
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StatusThe thesis was presented on the 24 May, 2007Approved by NCAA on the 14 June, 2007 Abstract – 0.37 Mb / in romanianThesisCZU 616.36-004-02-074:615.9+616-091.8
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Keywords
cathepsin L, liver, collagen degradation, hepatic cirrhosis regression, cathepsin B, cathepsin H, hydroxyproline, electron hystochemistrySummary
Some mechanisms of the connective tissue catabolism in liver during hepatic cirrhosis regression were investigated. It was studied the participation of cathepsin L, as well as other lisosomal proteinases, in the process of collagen degradation in liver.
Liver cirrhosis was induced in 140 white rats by a well known method of carbon tetrachloride (CCl4) injections for 13 weeks. Histological, electron-microscopical, electron-histochemical and biochemical investigations of the liver were effectuated at the stage of the maximal development of the liver cirrhosis and during two months of cirrhosis regression (at the 7-th, 14-th, 21-th, 30-th and 60-th day after the last injection of CCl4).
Histological investigations and biochemical determination of the hydroxyproline content in liver have shown that during the regression of experimental hepatic cirrhosis an intensive process of collagen degradation takes place. This process is maximal expressed during the first month after cessation of CCl4-treatment.
It was established that in the period of hepatic cirrhosis regression an important increase of the cysteine proteinases (cathepsins B, H and L) activity in liver took place. The dynamic of the enzymes activity had a phase character and shown a high correlation with tissue hydroxiproline level, that suggest a direct implication of the enzymes in the process of collagen degradation in liver.
Electron-histochimical study has detected the cathepsin L in normal liver in the lisosomes of the hepatocytes, Kupffer cells and endoteliocytes. It was shown, that during the hepatic cirrhosis regression cathepsin L is secreted by the hepatocytes, macrophages (Kupffer cells) and fibroblaste to the extracellular space for participation in the extracellular collagen degradation. The intensive extracellular collagen catabolism in liver during the cirrhosis regression is provided by the hepatocytes, but the intracellular collagen degradation is provided by the macrophage and fibroblasts with the active participation of cathepsin L.
Oficial Reviewers
- Ieremia Zota
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova - Ion Haidarlî
doctor habilitat, professor, Public Medical Sanitary Intitution Institute of Phthisiopneumology "Chiril Draganiuc"
Theses
