Influence of Liver Fibrosis on Lobular Zonation

  1. Ghallab, Ahmed ORCID logo
  2. Myllys, Maiju
  3. Holland, Christian ORCID logo
  4. Zaza, Ayham
  5. Murad, Walaa
  6. Hassan, Reham ORCID logo
  7. Ahmed, Yasser
  8. Abbas, Tahany
  9. Abdelrahim, Eman
  10. Schneider , Kai Markus ORCID logo
  11. Matz-Soja, Madlen ORCID logo
  12. Reinders, Jörg
  13. Gebhardt, Rolf
  14. Berres, Marie-Luise
  15. Hatting, Maximilian
  16. Drasdo, Dirk ORCID logo
  17. Saez-Rodriguez, Julio
  18. Trautwein, Christian
  19. Hengstler, Jan ORCID logo

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WeightNameValue
1000 Titel
  • Influence of Liver Fibrosis on Lobular Zonation
1000 Autor/in
  1. Ghallab, Ahmed |
  2. Myllys, Maiju |
  3. Holland, Christian |
  4. Zaza, Ayham |
  5. Murad, Walaa |
  6. Hassan, Reham |
  7. Ahmed, Yasser |
  8. Abbas, Tahany |
  9. Abdelrahim, Eman |
  10. Schneider , Kai Markus |
  11. Matz-Soja, Madlen |
  12. Reinders, Jörg |
  13. Gebhardt, Rolf |
  14. Berres, Marie-Luise |
  15. Hatting, Maximilian |
  16. Drasdo, Dirk |
  17. Saez-Rodriguez, Julio |
  18. Trautwein, Christian |
  19. Hengstler, Jan |
1000 Erscheinungsjahr 2019
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2019-12-02
1000 Erschienen in
1000 Quellenangabe
  • 8(12):1556
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2019
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3390/cells8121556 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953125/ |
1000 Ergänzendes Material
  • https://www.mdpi.com/2073-4409/8/12/1556#supplementary |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Little is known about how liver fibrosis influences lobular zonation. To address this question, we used three mouse models of liver fibrosis, repeated CCl4 administration for 2, 6 and 12 months to induce pericentral damage, as well as bile duct ligation (21 days) and mdr2−/− mice to study periportal fibrosis. Analyses were performed by RNA-sequencing, immunostaining of zonated proteins and image analysis. RNA-sequencing demonstrated a significant enrichment of pericentral genes among genes downregulated by CCl4; vice versa, periportal genes were enriched among the upregulated genes. Immunostaining showed an almost complete loss of pericentral proteins, such as cytochrome P450 enzymes and glutamine synthetase, while periportal proteins, such as arginase 1 and CPS1 became expressed also in pericentral hepatocytes. This pattern of fibrosis-associated ‘periportalization’ was consistently observed in all three mouse models and led to complete resistance to hepatotoxic doses of acetaminophen (200 mg/kg). Characterization of the expression response identified the inflammatory pathways TGFβ, NFκB, TNFα, and transcription factors NFKb1, Stat1, Hif1a, Trp53, and Atf1 among those activated, while estrogen-associated pathways, Hnf4a and Hnf1a, were decreased. In conclusion, liver fibrosis leads to strong alterations of lobular zonation, where the pericentral region adopts periportal features. Beside adverse consequences, periportalization supports adaptation to repeated doses of hepatotoxic compounds.
1000 Sacherschließung
lokal cytochrome P450
lokal acetaminophen
lokal bile duct ligation
lokal inflammation
lokal chronic liver disease
lokal liver lobule
lokal zonation
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-0695-3403|https://frl.publisso.de/adhoc/uri/TXlsbHlzLCBNYWlqdQ==|https://orcid.org/0000-0002-3060-5786|https://frl.publisso.de/adhoc/uri/WmF6YSwgQXloYW0=|https://frl.publisso.de/adhoc/uri/TXVyYWQsIFdhbGFh|https://orcid.org/0000-0002-6569-7676|https://frl.publisso.de/adhoc/uri/QWhtZWQsIFlhc3Nlcg==|https://frl.publisso.de/adhoc/uri/QWJiYXMsIFRhaGFueQ==|https://frl.publisso.de/adhoc/uri/QWJkZWxyYWhpbSwgRW1hbg==|https://orcid.org/0000-0002-0047-3794|https://orcid.org/0000-0002-5929-3704|https://frl.publisso.de/adhoc/uri/UmVpbmRlcnMsIErDtnJn|https://frl.publisso.de/adhoc/uri/R2ViaGFyZHQsIFJvbGY=|https://frl.publisso.de/adhoc/uri/QmVycmVzLCBNYXJpZS1MdWlzZQ==|https://frl.publisso.de/adhoc/uri/SGF0dGluZywgTWF4aW1pbGlhbg==|https://orcid.org/0000-0002-9995-5987|https://frl.publisso.de/adhoc/uri/U2Flei1Sb2RyaWd1ZXosIEp1bGlv|https://frl.publisso.de/adhoc/uri/VHJhdXR3ZWluLCBDaHJpc3RpYW4=|https://orcid.org/0000-0002-1427-5246
1000 Label
1000 Förderer
  1. Bundesministerium für Bildung und Forschung |
1000 Fördernummer
  1. 031L0052; 031L0045; 031L0049
1000 Förderprogramm
  1. LiSyM
1000 Dateien
  1. Influence of Liver Fibrosis on Lobular Zonation
    Influence of Liver Fibrosis on Lobular Zonation
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm LiSyM
    1000 Fördernummer 031L0052; 031L0045; 031L0049
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6420990.rdf
1000 Erstellt am 2020-05-18T14:38:27.093+0200
1000 Erstellt von 254
1000 beschreibt frl:6420990
1000 Bearbeitet von 122
1000 Zuletzt bearbeitet Wed May 20 09:46:58 CEST 2020
1000 Objekt bearb. Wed May 20 09:46:45 CEST 2020
1000 Vgl. frl:6420990
1000 Oai Id
  1. oai:frl.publisso.de:frl:6420990 |
1000 Sichtbarkeit Metadaten public
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