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Intracellular accumulation of incompletely processed transforming growth factor-alpha polypeptides in ground glass hepatocytes of chronic hepatitis B virus infection

Identifieur interne : 000213 ( Istex/Corpus ); précédent : 000212; suivant : 000214

Intracellular accumulation of incompletely processed transforming growth factor-alpha polypeptides in ground glass hepatocytes of chronic hepatitis B virus infection

Auteurs : Peter Schirmacher ; Dagmar Schau ; Hans Peter Dienes

Source :

RBID : ISTEX:777AF08BEA73B4FB9CE51B8A3903666CA72E25C5

Abstract

Background: Transforming growth factor-alpha is an intracellularly processed and secreted polypeptide that induces a proliferative response in epithelial target cells and represents a potential regulatory factor in embryonic development, liver regeneration, and also hepatocarcinogenesis. We have observed focal transforming growth factor-alpha expression in liver tissues with chronic hepatitis B virus infection. Methods: To further elucidate the nature of this focal transforming growth factor-alpha accumulation were have analyzed overall 23 different liver tissues with chronic hepatitis B virus and hepatitis C virus infection as well as normal liver tissues by immunohistology, ELISA, and Western immunoblot with and without immunoprecipitation. Results: By immunohistology transforming growth factor-alpha polypeptides showed focal subcellular accumulation in ground glass hepatocytes, the histological hallmark of chronic hepatitis B virus infection, in co-localization with HBV-preS1 antigen. By ELISA and Western immunoblot increased tissue concentrations of transforming growth factor-alpha were demonstrated in chronically hepatitis B virus-infected liver tissues with ground glass hepatocytes, especially a 15-kD polypeptide, most likely representing an incompletely processed transforming growth factor-alpha polypeptide. transforming growth factor-alpha retention in ground glass hepatocytes is not a general unspecific effect, since it was not observed for several other secretory liver proteins. Accumulated transforming growth factor-alpha in ground glass hepatocytes does not co-localize with Epidermal Growth Factor Receptor expression. Conclusion: Thus evidence is presented that a principally secreted (viral) polypeptide (HBV-preS1) can interfere with the secretion and processing of a second (cellular) protein (transforming growth factor-alpha). Accumulation of transforming growth factor-alpha may result from alteration of the endoplasmic reticulum due to storage of hepatitis B virus surface antigen particles. No evidence was found for transforming growth factor-alpha in ground glass hepatocytes to intracellularly interact with the Epidermal Growth Factor Receptor.

Url:
DOI: 10.1016/S0168-8278(96)80139-5

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ISTEX:777AF08BEA73B4FB9CE51B8A3903666CA72E25C5

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<abstract lang="en">Background: Transforming growth factor-alpha is an intracellularly processed and secreted polypeptide that induces a proliferative response in epithelial target cells and represents a potential regulatory factor in embryonic development, liver regeneration, and also hepatocarcinogenesis. We have observed focal transforming growth factor-alpha expression in liver tissues with chronic hepatitis B virus infection. Methods: To further elucidate the nature of this focal transforming growth factor-alpha accumulation were have analyzed overall 23 different liver tissues with chronic hepatitis B virus and hepatitis C virus infection as well as normal liver tissues by immunohistology, ELISA, and Western immunoblot with and without immunoprecipitation. Results: By immunohistology transforming growth factor-alpha polypeptides showed focal subcellular accumulation in ground glass hepatocytes, the histological hallmark of chronic hepatitis B virus infection, in co-localization with HBV-preS1 antigen. By ELISA and Western immunoblot increased tissue concentrations of transforming growth factor-alpha were demonstrated in chronically hepatitis B virus-infected liver tissues with ground glass hepatocytes, especially a 15-kD polypeptide, most likely representing an incompletely processed transforming growth factor-alpha polypeptide. transforming growth factor-alpha retention in ground glass hepatocytes is not a general unspecific effect, since it was not observed for several other secretory liver proteins. Accumulated transforming growth factor-alpha in ground glass hepatocytes does not co-localize with Epidermal Growth Factor Receptor expression. Conclusion: Thus evidence is presented that a principally secreted (viral) polypeptide (HBV-preS1) can interfere with the secretion and processing of a second (cellular) protein (transforming growth factor-alpha). Accumulation of transforming growth factor-alpha may result from alteration of the endoplasmic reticulum due to storage of hepatitis B virus surface antigen particles. No evidence was found for transforming growth factor-alpha in ground glass hepatocytes to intracellularly interact with the Epidermal Growth Factor Receptor.</abstract>
<subject>
<genre>Keywords</genre>
<topic>Growth factor</topic>
<topic>Hepatitis</topic>
<topic>Hepatitis B Virus</topic>
<topic>Hepatocytes</topic>
<topic>Transforming growth factor-alpha</topic>
</subject>
<relatedItem type="host">
<titleInfo>
<title>Journal of Hepatology</title>
</titleInfo>
<titleInfo type="abbreviated">
<title>JHEPAT</title>
</titleInfo>
<genre type="Journal">journal</genre>
<originInfo>
<dateIssued encoding="w3cdtf">199605</dateIssued>
</originInfo>
<identifier type="ISSN">0168-8278</identifier>
<identifier type="PII">S0168-8278(00)X0032-3</identifier>
<part>
<date>199605</date>
<detail type="volume">
<number>24</number>
<caption>vol.</caption>
</detail>
<detail type="issue">
<number>5</number>
<caption>no.</caption>
</detail>
<extent unit="issue pages">
<start>517</start>
<end>647</end>
</extent>
<extent unit="pages">
<start>547</start>
<end>554</end>
</extent>
</part>
</relatedItem>
<identifier type="istex">777AF08BEA73B4FB9CE51B8A3903666CA72E25C5</identifier>
<identifier type="DOI">10.1016/S0168-8278(96)80139-5</identifier>
<identifier type="PII">S0168-8278(96)80139-5</identifier>
<recordInfo>
<recordContentSource>ELSEVIER</recordContentSource>
</recordInfo>
</mods>
</metadata>
</istex>
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