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Altered Proteoglycan Gene Expression in Human Biliary Cirrhosis

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Pathology & Oncology Research

Abstract

Proteoglycans play key roles in the physiological assembly of extracellular matrices and in the modulation of growth factor activities. During liver regeneration there is a profound remodelling of the connective tissue network with a concurrent alteration in proteoglycan gene expression. In the present study we have analyzed in detail the biochemical and molecular properties of the proteoglycans associated with biliary cirrhosis. The three major proteoglycans of human liver, namely decorin, syndecan and perlecan, were markedly elevated in the cirrhotic parenchyma as compared to normal liver tissue. Particularly elevated (eight fold) was the perlecan. This proteoglycan had not only heparan sulfate but also chondroitin and der-matan sulfate. Reverse transcriptase PCR revealed a marked enhancement of decorin and syndecan expression and detectable message for perlecan was found only in the cirrhotic liver. These results indicate that significant proteoglycan alterations are associated with the development of biliary cirrhosis and provide basis for future studies aimed at the characterization of the molecular events involved in the regulation of extracellular matrix deposition in this common human disease.

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Abbreviations

bFGF:

basic fibroblast growth factor

BM:

basal membrane

CS:

chondroitin sulfate

CSPG:

chondroitin sulfate proteoglycan

DEPC:

diethyl pyrocarbonate

DS:

dermatan sulfate

ECM:

extracellular matrix

EDTA:

ethylenediaminetetraacetic acid

EHS:

Engelberth-Holm-Swarm

GAG:

glycosaminoglycan

HPLC:

high performance liquid chromatography

HS:

heparan sulfate

HSPG:

heparan sulfate proteoglycan

OD:

optical density

PG:

proteoglycan

RNA:

ribonucleic acid

TCA:

trichloroacetic acid

TFMS:

trifluoromethanesulfonic acid

TGF - β:

transforming growth factor beta-1

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Authors and Affiliations

  1. Semmelweis University of Medicine, First Institute of Pathology and Experimental Cancer Research, Philadelphia, USA

    Ilona Kovalszky, Julia O Nagy, Monika Gallai, Anna SebestyÉn, Zsuzsa Schafe, Sándor Paku & András Jeney

  2. Thomas Jefferson University, Philadelphia, USA

    Renato V. Iozzo

Authors
  1. Ilona Kovalszky
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  2. Julia O Nagy
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  3. Monika Gallai
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  4. Anna SebestyÉn
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  8. Renato V. Iozzo
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Additional information

This work was supported in part by grants ETT M59 from the Hungarian Ministry of Health and T 017085 from the National Scientific Research Foundation. Dr. Iozzo was supported by NIH grants CA-39481 and CA-47282 and is the recipient of a Faculty Research Award (FRA-376) from the American Cancer Society.

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Kovalszky, I., O Nagy, J., Gallai, M. et al. Altered Proteoglycan Gene Expression in Human Biliary Cirrhosis. Pathol. Oncol. Res. 3, 51–58 (1997). https://doi.org/10.1007/BF02893354

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  • DOI: https://doi.org/10.1007/BF02893354

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