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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagen synthesis was measured in liver slices obtained from mice with hepatosplenic schistosomiasis. Enlarged fibrotic livers from these mice contained 20 times more collagen than normal. This model of hepatic fibrosis results from an inflammatory granulomatous host response to Schistosoma mansoni ova in portal tracts, rather than from direct lover cell injury as with carbon tetrachloride-induced liver fibrosis. Collagen synthesis, as measured by the formation of labeled protein-bound hydroxyproline, occurred in granulomas isolated from fibrotic livers. Labeled collagen that cochromatographed with type I collagen was extracted with neutral salt solution from liver slices incubated with labeled proline. The free proline pool of the liver was doubled in infected mice; coordinately, liver slices from these animals showed maximal collagen production when the concentration of free proline in the medium was raised to 0.4 mM, the same level measured in the fibrotic livers. Under such conditions, collagen synthesis was at a rate equivalent to the formation of 5.4 nmol of protein-bound hydroxyproline per g liver in 6 h. In comparative incubations in medium containing 0.2 mM proline, fibrotic liver slices produced 16-fold more collagen than normal slices. The proline analogue, L-azetidine 2-carboxylic acid, effectively inhibited synthesis of labeled collagen by fibrotic liver slices. These studies show the synthesis of collagen in a reproducible animal model of the most prevalent form of human liver fibrosis. Difinitition of the controlling factors in this system is of interest for the general problem of fibrosis produced by immunological responses.
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PMID:Liver collagen synthesis in murine schistosomiasis. 84 55

It has been observed that Ito cells in vitro undergo phenotypical changes ("activation") similar to those noted in vivo during the development of liver fibrosis. Because conflicting data have been published on the amount and different types of collagens synthesized by Ito cells in vitro, collagen biosynthesis was studied at different "activation" stages on both the protein and RNA levels. Immunoprecipitation of endogenously labeled collagen showed that freshly isolated ("resting") Ito cells synthesize mainly collagen type IV. Collagen type I was hardly detectable in the earlier stage of primary culture, but it clearly increased starting 5 days after isolation. Compared with the basal rates measured at day 3 after isolation, collagen types I, III, and IV increased 7.5-, 3.5-, and 1.9-fold, respectively, until day 7 of culture. The relative ratios of newly synthesized collagen types I, III, and IV on day 3 after isolation were approximately 10%, 45%, and 45%, and they changed to 45%, 40%, and 15% on day 7 of primary culture. On the RNA level, freshly isolated Ito cells contained predominantly collagen type IV- and III-specific transcripts. By densitometric analysis, collagen type I, III, and IV messenger RNAs increased 6.2-, 2.5-, and 3.5-fold from day 3 to day 7 of primary culture. These results indicate that "resting" Ito cells synthesize primarily collagen type IV and could be a major cellular source of this basement membrane component in normal liver. "Activated" Ito cells switch to the synthesis of the interstitial collagen types I and III and might be mainly responsible for the accumulation of collagen types I and III in fibrotic liver diseases.
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PMID:Differential expression of collagen types I, III, and IV by fat-storing (Ito) cells in vitro. 156 93

Development and regression of liver fibrosis and cirrhosis induced by CCl4 in male F-344 rats were strictly followed during and after an 8-week treatment. The relative amount of collagen was measured by morphometry and the number of glycosaminoglycan (GAG) containing fat storing cells was counted at each time point. The expression of proteoglycan genes (decorin, versican and BPG-5 HSPG) was studied in parallel with the development of cirrhosis. Collagen content of the liver as well as the number of GAG-containing mesenchymal (fat storing) cells increased in parallel until two weeks after the cessation of CCl4 treatment. Later, both the collagen content and the number of GAG-containing cells decreased in parallel and significantly. Proteoglycan gene expression in the nonparenchymal fraction of liver cells indicated an active proteoglycan synthesis in the course of the development of cirrhosis. It is concluded that modified Ito (fat storing) cells synthesize proteoglycans and play an important role in the formation of connective tissue fibers in liver fibrosis.
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PMID:Role of the modified (glycosaminoglycan producing) perisinusoidal fibroblasts in the CCl4-induced fibrosis of the rat liver. 138 23

Collagen glucosyltransferase activity (EC 2.4.1.66) was quantified in experimentally-induced liver carcinoma, murine schistosomiasis mansoni-induced liver fibrosis and compared to the level of enzyme activity in control liver samples. Enzyme activity in hepatoma and fibrotic tissues were 12 and 5 times the mean level of enzyme activity in the control liver tissue respectively. The level of enzyme activity in the hepatoma tissue was two times the level of enzyme activity found in the fibrotic tissue. The findings in this study provide the basis for the highly elevated serum values of this intracellular enzyme in experimentally-induced primary hepatocellular carcinoma or in human primary hepatoma. The enzyme activity may be increased in primary liver carcinoma to compensate for an increased rate of collagen synthesis.
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PMID:Liver collagen glucosyltransferase in experimental primary liver carcinoma. 183 51

The effects of ethanol and its metabolites on collagen synthesis in cultured rat Ito cells and hepatocytes were studied. In cultured Ito cells, collagen synthetic ability reached peak values after incubation for 24 h and after 8 h in cultured hepatocytes. The distribution patterns of 14C-activity in each collagen fraction were quite different between the two cell types. About 80% of the activity was found in the degraded collagen fraction in the cultured hepatocytes, indicating a rapid turn-over of collagen protein in this cell type. In the Ito cells, the activity in the intact collagen was about 50%. Ethanol and its metabolites added to the incubation medium did not stimulate collagen synthesis in either cell type; rather, they inhibited it. Collagen metabolism in the cells to which ethanol or its metabolites had been added was slower than in the control medium. These results indicate that the pathogenesis of alcoholic liver fibrosis is not simple and that interaction or modulation of cell function in different types of cells should be considered when examining the mechanisms of fibrogenesis in alcoholic liver fibrosis.
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PMID:Effects of ethanol and its metabolites on collagen synthesis by cultured rat liver cells. 249 Nov 50

Rats receiving intravenous injection of human albumin (4 mg/rat) once biweekly developed liver fibrosis. The lesion seemed to have little relation to hepatocellular injury. The incidence of liver fibrosis increased with the length of immunization, ranging 80%-86% after 30-60 days. The whole process of experimental liver fibrosis may be divided into three phases. The first is the initial stage of fibroplasia (from the first day to the time of 15 days after start of immunization). In this phase, Ito cells were activated and collagen type I and type III began to increase. The second is the activated stage of fibroplasia (from the 15th to the 60th day after the beginning of immunization), in which collagen type I and type III reached the maximum and myofibroblasts as well as 'transitional cells' proliferated with deposition of collagen fibers. The third phase is the stage of post-fibroplasia (the period after elimination of immunization). Collagen type III diminished gradually while collagen type I remained increasing. Our findings indicated that fibroplasia occurs at the very beginning of liver injury. This suggest that treatment of liver fibrosis must be considered simultaneously with treatment of acute hepatitis.
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PMID:[Morphological observations of collagen type I and type III in experimental liver fibrosis]. 277 59

In an attempt to elucidate the role of fat-storing cells (FSCs) in alcoholic liver fibrosis, we examined the effects of ethanol and acetaldehyde on collagen synthesis by FSCs isolated from CCl4-treated or normal rats. Isolated FSCs from normal rats showed characteristic lipid droplets in the cytoplasm. FSCs from CCl4-treated rats showed an abundant rough endoplasmic reticulum and a small number of lipid droplets. Collagen synthesis by the cells from CCl4-treated rats was 4-5-fold enhanced as compared with untreated rats. Though ethanol had an inhibitory effect on collagen synthesis by FSCs, acetaldehyde stimulated collagen production by the cells from CCl4-induced hepatic fibrosis, whereas collagen synthesis by the cells from normal rats was not influenced by acetaldehyde. From these results, FSCs are morphologically and functionally changed in liver fibrosis, and the transitional state of FSCs might be important in the pathogenesis of alcoholic liver fibrosis.
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PMID:Effect of acetaldehyde on collagen synthesis by fat-storing cells isolated from rats treated with carbon tetrachloride. 377 50

Primary cultures and cell lines were established from suspensions of purified fat-storing cells isolated from the rat liver. When seeded at a suitable density, fat-storing cells in primary culture reached confluency in 3 to 4 days and could be transferred and established as cell lines for at least two passages. The typical morphological characteristics of fat-storing cells in vivo were retained in the cells during primary culture. Vitamin A fluorescence was still associated with lipid droplets of cells in culture up to and including the second passage. Investigation of the cytoskeletal structure by indirect immunofluorescence showed the presence of vimentin, actin and tubulin in the cells; no alpha-prekeratin was present. The presence of vimentin suggested a fibroblastic or possible myogenic origin for fat-storing cells. The presence of connective tissue components in fat-storing cells in culture was demonstrated by indirect immunofluorescence. Collagen Types I and IV and laminin were present intracellularly in small granules in fat-storing cells in primary culture and in the first passage. Cells in the fourth passage contained only collagen Type 1. Fibronectin was only aligned extracellularly along the cell membrane, which did not exclude an extracellular source. Rat liver fat-storing cells in culture show a high proliferating capacity. Cell multiplication during prolonged culture was associated with phenotypic transition to a more fibroblastic appearance and gradual disappearance of vitamin A. These results indicate that fat-storing cells may be among the cell types involved in pathological changes observed during development of liver fibrosis.
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PMID:Purified rat liver fat-storing cells in culture divide and contain collagen. 637 50

Type VI collagen is a minor but essential matrix component in the liver. In this study, we utilized an acute and a chronic injury model to clarify the process of liver fibrosis in rats by administration of carbon tetrachloride. Collagen gene expression, with particular emphasis on type VI collagen, was studied by molecular hybridization techniques. The alpha 2(VI) collagen mRNA levels were markedly elevated on day 3 of acute injury and were approximately at the same high level at 7 and 14 weeks of chronic injury, as determined by Northern hybridizations and slot-blot analyses. Marked enhancement of type I collagen gene expression was similarly noted at these time points. The activation of collagen gene expression in acute injury, as determined by in situ hybridization, was particularly prominent in the vicinity of the central veins. Indirect immunofluorescence demonstrated marked accumulation of type VI collagen protein as early as day 3 of acute injury, and the reaction appeared to be initiated in the proximity of central veins. These results indicate that type VI collagen gene expression, together with other connective tissue components, including type I collagen, is activated in the early stages of the fibrotic process. Type VI collagen accumulation may contribute to the distorted architecture and functional impairment of the liver in hepatic fibrosis.
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PMID:Type VI collagen gene expression in experimental liver fibrosis: quantitation and spatial distribution of mRNAs, and immunodetection of the protein. 779 42

Collagen synthesis and degradation in normal and carbon-tetrachloride-injured male Wistar rats at early and late stages of liver fibrosis, and the potential beneficial effects of zinc supplementation on liver fibrogenesis and collagenolysis have been assessed by measuring hepatic collagen content and prolyl hydroxylase and collagenase activities. No significant changes in hepatic collagen and prolyl hydroxylase activities were observed between control rats (82 +/- 25 cpm/mg protein) and rats with induced cirrhosis (107 +/- 23 cpm/mg protein) after 4 weeks of carbon tetrachloride injury. By this time, hepatic collagenase activity was significantly lower in rats with induced cirrhosis (61 +/- 9 micro units/mg protein) than in control rats (133 +/- 31 micro units/mg protein) (p < 0.05). This result was prevented by zinc administration, since hepatic collagenase activity was similar in zinc-supplemented, carbon-tetrachloride-injured rats and normal rats (148 +/- 19 micromicrons/mg protein). After 16 weeks, all carbon-tetrachloride-injured rats had cirrhosis. Hepatic collagen content and prolyl hydroxylase activity were significantly higher in carbon-tetrachloride-injured rats than in controls. These effects were partially prevented by zinc administration, since only two of the seven zinc-supplemented, carbon-tetrachloride-injured rats had cirrhosis. Moreover, prolyl hydroxylase activity was significantly lower in zinc-supplemented injured rats (263 +/- 27 cpm/mg protein) than in the non-supplemented respective controls (389 +/- 52 cpm/mg protein) (p < 0.05). No significant changes in hepatic collagenase activity were observed at this stage of liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrogenic and collagenolytic activity in carbon-tetrachloride-injured rats: beneficial effects of zinc administration. 783 96


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