An experimental study of the pathogenesis and reversibility of schistosomal hepatic fibrosis

Cameron, G. R.; Ganguly, N. C.

doi:10.1002/path.1700870202

Cited by 41 publications

(16 citation statements)

References 33 publications

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“…The data are consistent with the model proposed by Phang et al (30) for saturable transport of proline into a collagensynthesizing compartment in fetal rat calvaria. The decreased proline specific activity noted in the medium after 6 h is consistent with equilibration of proline in the medium and in liver slices, and with possible synthesis of new unlabeled proline by the slices. The comparative incubations of fibrotic and normal liver slices were performed at a concentration of 0.2 mM free proline in the medium, equivalent to the free proline pool measured in normal liver.…”

Section: Discussionsupporting

confidence: 71%

“…Periportal fibrosis is the major disturbance during most of the course of this disease. Mice infected with S. mansoni cercariae provide an experimental model of liver collagen deposition whose course resembles that of the human disease (6,7). In contrast to CCl4-induced liver fibrosis in rats, the (11) produced with a multiple-chamber reservoir as described by Piez and Morris (12).…”

Section: Introductionmentioning

confidence: 99%

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Liver collagen synthesis in murine schistosomiasis.

Dunn¹,

Rojkind²,

Warren³

et al. 1977

J. Clin. Invest.

106

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A B S T R A C T 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 liver 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. Definitition of the controlling factors in this system is of interest for the general problem of fibrosis produced by immunological responses.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Liver collagen synthesis in murine schistosomiasis.

Dunn¹,

Rojkind²,

Warren³

et al. 1977

J. Clin. Invest.

106

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“…3 Histologic and ultrastructural changes associated with degradation of fibrosis after curative treatment have been described in humans 4 and in experimental animals infected with Schistosoma mansoni. [5][6][7] Degradation of early fibrosis in hepatic periovular granulomas formed during an 8-12-week mouse infection starts a few days after treatment and is almost complete after 2-4 months. 5,8 However, in granulomas formed during prolonged experimental infections and in human pipestem portal fibrosis, partial or total resorption of fibrosis takes a prolonged time, usually more than four months in the mouse 5 and 2-3 years in humans with schistosomal hepatosplenic disease.…”

mentioning

confidence: 99%

Expression of metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in schistosomal portal fibrosis.

Gómez

Lorenzo²,

Alonso³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Focal extracellular matrix degradation morphologically identified in human portal pipestem fibrosis due to Schistosoma mansoni did not express immunohistochemical reactivity for metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2). However, when active schistosomal periovular granulomas were present, a strong reactivity for MMP-1, MMP-2, TIMP-1, and TIMP-2 was observed. No reactivity was ever observed for MMP-9. However, the positive pattern of immunohistochemical expression was not seen in old fibrotic periovular granulomas, which were sometimes situated in other areas of the same microscopic section. Positive staining for MMPs and TIMPs was observed at the same time in hepatocytes and within the apical portion of bile duct epithelium. These findings are consistent with the concept that matrix degradation in recent and old fibroses, in addition to differing at the ultrastructural level, also differs in immunohistochemical expression of metalloproteinases and their inhibitors.Extracellular matrix degradation occurs in several physiologic and pathologic conditions. In human portal fibrosis due to schistosomiasis, resorption of fibrous tissue may be quite impressive, since a large amount of hepatic fibrosis can disappear a few years following curative chemotherapy.

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“…18,19 But, then studies appeared demonstrating that such data were valid for recent schistosomiasis (8-10 weeks after the cercaria exposure), and fibrosis of the delayed infections ( 16-20 weeks) were irreversible. 20 These data indicated that recent disease is reversible and the delayed one is irreversible.…”

Section: The Reversibility Of Hepatic Fibrosis In Schistosomiasismentioning

confidence: 95%

Is cirrhosis of the liver reversible?

Kumar

Sarin

2007

Indian J Pediatr

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Extensive and persistent hepatic fibrosis has for a long time been considered irreversible. Accumulating evidence suggests that liver fibrosis is reversible and that recovery from cirrhosis may be possible. The application of molecular techniques to models of reversible fibrosis are helping to establish the events and processes that are critical to recovery. The problem consists in identifying and eliminating its cause. Although fibrosis in the liver has little functional significance by itself, its severity derives from associated vascular changes. Disappearance of fibrosis can be accompanied by remodeling of vascular changes. However, depending on its duration, the fibrosis may be irreversible.

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An experimental study of the pathogenesis and reversibility of schistosomal hepatic fibrosis

Cited by 41 publications

References 33 publications

Liver collagen synthesis in murine schistosomiasis.

Liver collagen synthesis in murine schistosomiasis.

Expression of metalloproteinases (MMP-1, MMP-2, and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in schistosomal portal fibrosis.

Is cirrhosis of the liver reversible?

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