Dynamics of hepatic glycosaminoglycan accumulation in murine Schistosoma japonicum infection

Olds, G R; Finegan, Candace K.; Kresina, Thomas F.

doi:10.1016/0016-5085(86)90184-8

Cited by 13 publications

(7 citation statements)

References 30 publications

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“…In order of decreasing concentrations, they are heparan sulfate (more than 60% of total GAG), dermatan sulfate and chondroitin-4,6-sulfate isomers (5-8, 12). The amount of sulfated PGs in normal liver tissue is low but in pathologic states such as fibrosis (6)(7)(8)13) and HCC (14,15) their concentration increases several times and the profile of GAGs changes, dramatically, leading to a strong absolute and relative increase of dermatan sulfate and chondroitin sulfate and a fractional decrease of heparan sulfate (lower than 50% (25). The core protein sequences of the members of this family of leucine-rich-motif extracellular proteins have been postulated to play a role in molecular interactions and specifically to facilitate the binding of these macromolecules to other matrix components such as collagens (25-29) and fibronectins (30-32).…”

Section: (Hepatology 1992; 16~204-2 16)mentioning

confidence: 99%

“…In order of decreasing concentrations, they are heparan sulfate (more than 60% of total GAG), dermatan sulfate and chondroitin-4,6-sulfate isomers (5-8, 12). The amount of sulfated PGs in normal liver tissue is low but in pathologic states such as fibrosis (6)(7)(8)13) and HCC (14,15) their concentration increases several times and the profile of GAGs changes, dramatically, leading to a strong absolute and relative increase of dermatan sulfate and chondroitin sulfate and a fractional decrease of heparan sulfate (lower than 50%). Fat-storing cells (FSCs) (also called perisinusoidal lipocytes, vitamin A-storing cells or It0 cells [16,171) and their transformed counterpart (i.e.…”

mentioning

confidence: 99%

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Biglycan and Decorin Gene Expression in Normal and Fibrotic Rat Liver: Cellular Localization and Regulatory Factors

et al. 1992

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The expression of genes encoding the core proteins of the novel small chondroitin/dermatan sulfate proteoglycans decorin and biglycan was studied in the livers of normal rats and in liver tissue during fibrogenesis induced by prolonged bile-duct ligation and thioacetamide poisoning. The cell types responsible for the expression of these transcripts and some key regulatory factors were identified. Both biglycan and decorin messenger RNAs were detected in normal liver tissue. Their relative abundance increased strongly during liver fibrogenesis, reaching highest levels in cirrhotic tissue 8 wk after common bile-duct ligation and after 12 wk of peroral thioacetamide administration, respectively. Specific proteoglycan transcripts were almost absent in hepatocytes from normal and regenerating liver, and only trace amounts were observed in freshly isolated and cultured Kupffer cells. Fat-storing cells clearly expressed both biglycan and decorin transcripts. The steady-state levels of their messenger RNAs increased threefold (biglycan) and fourfold (decorin) during primary culture. Myofibroblastlike cells (transformed fat-storing cells after the second passage) contained dramatically reduced levels of decorin messenger RNA and also lower levels of biglycan messenger RNA compared with primary cultures. These changes of core protein messenger RNA expression were not reflected by the synthesis rates of medium proteoglycans labeled with 35S as Na2SO4, in particular that of medium chondroitin sulfate. Transiently acidified (but not native) conditioned media from Kupffer cells and myofibroblastlike cells and transforming growth factor-beta 1 enhanced the relative abundances of biglycan and decorin messenger RNAs up to five times in primary-cultured fat-storing cells. Biglycan and decorin in myofibroblastlike cells did not respond to these stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: (Hepatology 1992; 16~204-2 16)mentioning

confidence: 99%

“…In order of decreasing concentrations, they are heparan sulfate (more than 60% of total GAG), dermatan sulfate and chondroitin-4,6-sulfate isomers (5-8, 12). The amount of sulfated PGs in normal liver tissue is low but in pathologic states such as fibrosis (6)(7)(8)13) and HCC (14,15) their concentration increases several times and the profile of GAGs changes, dramatically, leading to a strong absolute and relative increase of dermatan sulfate and chondroitin sulfate and a fractional decrease of heparan sulfate (lower than 50%). Fat-storing cells (FSCs) (also called perisinusoidal lipocytes, vitamin A-storing cells or It0 cells [16,171) and their transformed counterpart (i.e.…”

mentioning

confidence: 99%

Biglycan and Decorin Gene Expression in Normal and Fibrotic Rat Liver: Cellular Localization and Regulatory Factors

et al. 1992

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“…Aliquots of 50 granulomas were removed by Past,eur pipet with the aid of a dissecting microscope (11 j and used for subsequent studies. Thin liver slices from infected and noninfected mice were obtained as described previously (12 (13,14). As shown in previous studies (14), radioactivity isolated in this fashion is associated with hepatic glycosaminoglycans.…”

Section: Isolation Of Hepatic Granulomas and Liver Slicesmentioning

confidence: 99%

“…Thin liver slices from infected and noninfected mice were obtained as described previously (12 (13,14). As shown in previous studies (14), radioactivity isolated in this fashion is associated with hepatic glycosaminoglycans. The digests were chilled and treated with 10% trichloroacetic acid to remove the protein.…”

Section: Isolation Of Hepatic Granulomas and Liver Slicesmentioning

confidence: 99%

Dynamics of hepatic connective tissue matrix constituents during murine schistosoma mansoni infection

1989

Self Cite

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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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“…Neither glycosaminoglycan synthesis nor secretion in cultures of parenchymal and other non-parenchymal cells were evaluated under comparable conditions. Information on the relative contribution of the various cell types to hepatic proteoglycan and hyaluronate synthesis will be important since under pathological conditions like liver fibrosis (25)(26)(27)(28) and hepatocellular carcinoma (29,30), both the total glycosaminoglycan content and the pattern of suiphated and non-sulphated glycosaminoglycans chanige greatly. In the present study we attempted to compare the synthesis, secretion, and molecular profile of glycosaminoglycans of hepatocytes, fat-storing cellSj and Kupffer cells kept in culture under largely identical conditions.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Sulphated Glycosaminoglycan and Hyaluronate Synthesis and Secretion in Cultured Hepatocytes, Fat Storing Cells, and Kupffer Cells

Gressner¹,

Schäfer²

1989

Clinical Chemistry and Laboratory Medicine

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Summary:The extracellular matrix of normal liver contains several types of proteoglycans including heparan sulphate, chondroitin sulphate isomers, dermatan sulphate, and the glycosaminoglycan, hyaluronic acid. In the present study both the synthesis and secretion äs well äs the pattern of radioactively labeled proteoglycans and hyaluronic acid of hepatocytes, fat-storing cells (Ito cells), and Kupffer cells maintained in monolayer cultures under mostly identical conditions were compared to assess their relative contribution to hepatic proteoglycan synthesis. Fat-storing cells were identified äs the main type of cell producing and secreting proteoglycan and hyaluronic acid. More than 70% of labeled proteoglycan and hyaluronic acid were secreted into the medium. Heparan sulphate is the main type of proteoglycan in hepatocytes, whereas in the medium of fat-storing cells, chondroitin sulphate and dermatan sulphate comprise the mäjor fractions. Hyaluronic acid was not detectable in hepatocyte cultures and found only in low amounts in the medium of Kupffer cells. The results point to a stringent quantitative and qualitative cellular compartmentation of proteoglycan synthesis in liver with fat-storing cells äs the most important cell type for matrix proteoglycan and hyaluronic acid production.

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Dynamics of hepatic glycosaminoglycan accumulation in murine Schistosoma japonicum infection

Cited by 13 publications

References 30 publications

Biglycan and Decorin Gene Expression in Normal and Fibrotic Rat Liver: Cellular Localization and Regulatory Factors

Biglycan and Decorin Gene Expression in Normal and Fibrotic Rat Liver: Cellular Localization and Regulatory Factors

Dynamics of hepatic connective tissue matrix constituents during murine schistosoma mansoni infection

Comparison of Sulphated Glycosaminoglycan and Hyaluronate Synthesis and Secretion in Cultured Hepatocytes, Fat Storing Cells, and Kupffer Cells

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