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

Hepatic fibrosis is the major clinical sequela of infection with the helminth Schistosoma mansoni. However, little is known regarding its dynamics and regulation in schistosomiasis. The present study presents the dynamics of deposition and resorption of two major extracellular matrix components of fibrosis, glycosaminoglycans and collagens, during the course of experimental S. mansoni infection. Early in infection (6 weeks), glycosaminoglycan biosynthesis was markedly elevated, as was collagen biosynthesis. This led to significant accumulations of these two molecules at a glycosaminoglycan/collagen ratio similar to that observed in livers of uninfected mice (uronic acid/hydroxyproline ratio of 1.10 at 6 weeks compared to normal value of 1.25). During maximal hepatic fibrosis (12 to 18 weeks), both collagen and glycosaminoglycan biosynthesis continued to increase but the extracellular matrix shifted to a lower glycosaminoglycan/collagen ratio of 0.42, suggesting enhanced glycosaminoglycan breakdown. In addition, during this acute stage of infection, Type I collagen was the predominant isotype synthesized, whereas total collagenolytic activity degrading Type I collagen was maximal. During chronic infection, a decrease in the content of both hepatic glycosaminoglycans and collagens were noted, with a glycosaminoglycan/collagen ratio of 0.63. Decreased glycosaminoglycan content paralleled diminished biosynthetic rates. On the other hand, an over 50% reduction in collagen content (from 18 to 24 weeks) appeared not to result from diminished biosynthesis but from a switch in the predominant collagen isotype synthesized (from Type I to Type III), matched by an enhanced constitutive collagenolytic activity directed toward this type of collagen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dynamics of hepatic connective tissue matrix constituents during murine Schistosoma mansoni infection. 253 98

Prolyl hydroxylase (PH) is an enzyme acting in early stage of collagen synthesis. We have emphasized the significance of the measurement of serum PH (SIRPH) in relation to liver fibrosis mainly in patients with alcoholic liver disease (ALD). In this study, we determined the localization and positivity of PH by tissue PH stain method (Avidin Biotin Complex method) to clarify the differences in fibrosis between ALD (25 cases) and non-alcoholic liver diseases (non-ALD, 47 cases). Tissue PH was found to be positive in liver cells around Glisson's sheath in early stage of fibrosis, and then in liver cells left within septa and also in mesenchymal cells in the sinusoidal wall as fibrosis progressed. Although there were basically no marked differences between ALD and non-ALD, ALD tended to show stronger tissue PH positivity for a degree of fibrosis, PH positivity in parenchymal cells was especially remarkable around pericellular fibrosis in ALD. These results clearly reflected the important role of liver parenchymal cells in progression of fibrosis.
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PMID:[A histological examination of liver fibrosis and tissue prolyl hydroxylase in various liver diseases]. 255 96

Chondroitin sulfate/dermatan sulfate proteoglycans were obtained from the secretions of cultured rat hepatic lipocytes. The collagen-binding small proteoglycan II represented only a minor species (less than 10%), whereas similar amounts of small proteoglycan I and of a novel collagen-binding proteoglycan with a core protein of 101 kDa were found. These results support the concept of a special role of lipocytes in the pathogenesis of liver fibrosis.
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PMID:Biosynthesis of small proteoglycans by hepatic lipocytes in primary culture. 259 88

An animal model of liver fibrosis was produced by means of albumin immunization. Human serum albumin was given subcutaneously to immunize the rats with a dose of 4 mg, for 4 times. Then a booster dose was given through the caudal vein of rats in which albumin antibodies had been produced. Liver fibrosis and cirrhosis was formed in 85.5% of the animals. The increase of collagen content in liver tissue was parallel with the pathological grading of fibrosis. Reabsorption of fibrous tissue in this model occurred much later than in CC14 model. Subcutaneous administration of PGE1 could effectively protect the rats from anaphylactoid shock due to bigger booster dose. In regard to the mechanism of fibrosis, study with electronic microscopy, immunofluorescence histology, detection of serum C1q and C3 suggested that liver fibrosis results from proliferation of lipocytes, which was promoted by the formation of albumin and immune complex, and excessive secretion of collagen.
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PMID:[Animals with liver fibrosis induced by albumin immunization]. 263 26

Liver fibrosis and extracellular matrix play a central role in liver function impairment. Little information is available on the dynamic aspects and the natural history of fibroplasia, even if there is growing evidence that extracellular matrix accumulation (collagen I, III, IV, fibronectin, laminin, proteoglycans, etc.) is not to be considered only a passive structural support for damaged hepatic tissue, but may actively modulate liver cell behaviour. Clinicians need to date liver fibrosis and to monitor connective tissue synthesis and degradation, but attempts to develop reliable serological markers for collagen metabolism are hampered by the absence of a well defined golden standard to validate them. Nevertheless, serum type III aminoterminal procollagen peptide, at the moment, seems to be the most acceptable parameter of fibrogenesis. The data concerning the mechanisms of collagen production-degradation are becoming so precise and numerous that even if they have not, to date, led to 'routine' advantages for patients, they will end up becoming important tools in the clinical practice and management of liver fibrosis.
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PMID:Liver fibrosis and extracellular matrix. 264 66

We developed a competitive enzyme-immunoassay for serum type IV collagen peptide as a marker of fibrogenesis, and examined the relationship between serum type IV collagen peptide and hepatic disorder in CCl4-treated rats. The rats were treated for 8 weeks and signs of liver damage began to appear from about week 2. With the progression of these signs to liver fibrosis, type IV collagen increased in the fibrous septa and especially in the perisinusoidal walls, where the increase was manifested as development of a real basement membrane beneath the sinusoidal endothelial cells. In CCl4-treated rats, serum type IV collagen peptide significantly increased with the progression of liver fibrosis. When CCl4 administration was stopped, the collagen peptide rapidly decreased without any rebound rise. An intimate relationship was found between the production of serum type IV collagen peptide and liver prolyl hydroxylase activity and the amount of collagen deposited in the liver. These results suggest that serum type IV collagen peptide will be a useful biochemical marker for the early detection of fibrogenesis in the liver.
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PMID:Increased serum type IV collagen peptide in carbon tetrachloride-treated rats. 271 35

Serum procollagen-III-peptide (PP III) concentrations were measured in 54 patients with Crohn's disease and compared with data obtained from healthy controls and patients with liver fibrosis or ulcerative colitis. Whereas in alcoholic liver cirrhosis and chronic active hepatitis PP III was increased up to 18-fold as described by others, only 3 patients with Crohn's disease had slightly elevated PP III concentrations. In 2 of them, increased PP III could be explained by adolescence. In 5 other patients, PP III levels were at the upper limit of normal. Subgroup analysis showed that high clinical disease activity, recurrence after intestinal resection, presence of strictures and long disease duration did not elevate PP III levels. We therefore conclude that determination of serum PP III is of no value in the follow-up patients with Crohn's disease. In ulcerative colitis, PP III levels were uniformly normal. An additional result was a decreased PP III during corticosteroid therapy, suggesting a direct effect on collagen metabolism.
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PMID:[Procollagen-III-peptide in the serum of patients with Crohn disease]. 271 33

Immunofluorescence techniques were used to examine the distribution of Types I, III, IV and V collagen and fibronectin in the liver biopsy specimens from children with congenital liver fibrosis (CLF), extrahepatic portal blood circulation block, and cirrhosis developed following viral hepatitis. Both common patterns and characteristic features of the development of sclerotic processes were established. The common feature is the development of periportal connective tissue (CT) fibrosis mainly at the expense of Types I, III and V collagen and the accumulation of Types I, III, IV, V collagen and fibronectin in the walls of sinusoids during their "collagenization". The distinctive characteristic of posthepatic cirrhosis is the location of fibronectin and Type IV collagen in fibrous CT. Characteristic of CLF is high fibronectin concentrations in the areas of CT neoplasms along the periphery of portal tracts.
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PMID:[Collagen and fibronectin of the liver in children with congenital fibrosis, an extrahepatic portal circulation block and post-hepatitis cirrhosis (an immunohistochemical study)]. 274 28

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

Hepatic fibrosis was induced in rats by repeated i.p. injections of pig serum. The hepatic hydroxyproline content increased to 2.1 times the normal control level at 6 weeks and to 3.2 times at 10 weeks. When P-1894B, an inhibitor of prolyl hydroxylase, was administered, there was a dose-dependent inhibition of the increase to nearly normal control levels at 6 and 10 weeks. There was also by histology a dose-dependent reduction in the degree of hepatic fibrosis. Hepatocellular damage was minimal and its extent did not vary with the degree of fibrosis or the treatment. P-1894B dose dependently reduced the hydroxylation of peptidyl proline in the fibrotic liver. These data suggest that P-1894B inhibited hepatic fibrogenesis by direct action on collagen but not by protection against hepatocellular damage leading to collagen formation. A prolyl hydroxylase inhibitor may be a candidate for use in treatment of hepatic fibrosis.
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PMID:Decreased collagen accumulation by a prolyl hydroxylase inhibitor in pig serum-induced fibrotic rat liver. 283 4


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