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Up‐regulation of type I procollagen C‐proteinase enhancer protein messenger RNA in rats with CCl 4 ‐induced liver fibrosis
Author(s) -
Ogata I,
Auster A S,
Matsui A,
Greenwel P,
Geerts A,
D'Amico T,
Fujiwara K,
Kessler E,
Rojkind M
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510260312
Subject(s) - microbiology and biotechnology , messenger rna , biology , procollagen peptidase , rna , hepatic stellate cell , complementary dna , gene expression , gene , endocrinology , biochemistry
Using a polyclonal antibody raised against a liver stellate cell (LSC) line derived from a rat CCl 4 ‐cirrhotic liver, we isolated 14 clones from a complementary DNA library prepared with total RNA extracted from the same cell line, with nucleotide sequences homologous to that of the type I procollagen C‐proteinase enhancer protein (PCPE) gene. The longest PCPE insert of 1,530 base pairs contained an open reading frame coding for 468 amino acids. PCPE cDNA recognized by Northern blot a 1.7‐kilobase messenger RNA (mRNA) in total RNA extracted from freshly isolated and early passaged LSC, LSC lines derived from normal (NFSC) and cirrhotic (CFSC) rat livers, and various LSC clones derived from CFSC. The expression of PCPE mRNA was increased threefold in CFSC compared with NFSC. PCPE mRNA was not detected in total rat liver, freshly isolated hepatocytes, or endothelial or Kupffer cells. However, the expression of PCPE mRNA was induced in fibrotic livers of rats treated with CCl 4 . PCPE mRNA expression in LSC was up‐regulated by transforming growth factor β1 (TGF‐β1) and down‐regulated by tumor necrosis factor α (TNF‐α), similar to the changes in α1 (1) procollagen mRNA induced by these cytokines. PCPE was not detectable in liver biomatrix proteins obtained from normal liver. However, PCPE was increased in liver biomatrix proteins from cirrhotic livers and was proportional to the amount of collagen. These data suggest that PCPE may play an important role in the processing of type I collagen during liver fibrogenesis, and that TGF‐β1 and TNF‐α regulate its expression.