Modulation of collagen XVIII/endostatin expression in lobular and biliary rat liver fibrogenesis

• Published in: Journal of hepatology 2001-09, Vol.35 (3), p.386-391
• Main Authors: Jia, Ji-Dong, Bauer, Michael, Sedlaczek, Nicolai, Herbst, Hermann, Ruehl, Martin, Hahn, Eckhart G, Riecken, Ernst Otto, Schuppan, Detlef
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Biological and medical sciences; Carcinoma, Fibrosis; Collagen - genetics; Collagen Type XVIII; Digestive system; Endostatins; Gene Expression Regulation; Hepatocytes - metabolism; Investigative techniques, diagnostic techniques (general aspects); Liver; Liver Cirrhosis, Experimental - metabolism; Male; Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peptide Fragments - genetics; Procollagen; Procollagen - genetics; Rats; Rats, Wistar; RNA, Messenger - analysis; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue inhibitor of metalloproteinases
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(01)00134-9

Background/Aims : The liver is the major source of collagen XVIII (C18), the precursor of the angiogenesis inhibitor endostatin. In human liver C18 is mainly expressed by hepatocytes. However, its quantitative and temporospatial expression patterns during liver fibrogenesis are unknown. Methods : We used RNA quantification and in situ hybridization combined with cell-specific markers to study C18 compared to procollagen α1(I) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA expression in acute (single dose of CCl 4) and chronic (biliary) rat liver fibrogenesis. Results : C18 transcripts were only found in hepatocytes and bile duct epithelia of normal and fibrotic livers, and occasionally in arterial myocytes and hepatic stellate cells. 72 h after CCl 4 injection, C18 mRNA levels remained unchanged, while procollagen α1(I) mRNA was increased at 72 h and TIMP-1 mRNA peaked at 12 h ( P