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Cited by 90Liver physiology and pathologyHepatocellular Carcinoma Treatment and PrognosisOrgan Transplantation Techniques and Outcomes

Liver Zonation in Health and Disease: Hypoxia and Hypoxia-Inducible Transcription Factors as Concert Masters

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Kietzmann, Thomas·2019·International Journal of Molecular Sciences
DOI 10.3390/ijms20092347PMC PMC6540308
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Abstract

The liver and its zonation contribute to whole body homeostasis. Acute and chronic, not always liver, diseases impair proper metabolic zonation. Various underlying pathways, such as β-catenin, hedgehog signaling, and the Hippo pathway, along with the physiologically occurring oxygen gradient, appear to be contributors. Interestingly, hypoxia and hypoxia-inducible transcription factors can orchestrate those pathways. In the current review, we connect novel findings of liver zonation in health and disease and provide a view about the dynamic interplay between these different pathways and cell-types to drive liver zonation and systemic homeostasis.

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  • In zone 3, there is a well-known histologic pattern of liver damage in diseases that culminate in HCC, and zone 3 is frequently associated with oxidative stress.

    “In zone 3, there is a well-known histologic pattern of liver damage in diseases that culminate in HCC (61, 62), and zone 3 is frequently associated with oxidative stress (63, 64).”

    From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [63]

    Section 2 identifies zone 3 as the perivenous zone, and Section 9.1 says hepatocellular injury in NASH is mainly perivenous and discusses ROS-mediated lipid oxidation in disease progression. Section 10 links NAFLD and ALD to progression toward HCC. The paper does not establish a general histologic pattern across diseases that culminate in HCC or state that zone 3 is frequently associated with oxidative stress. (LLM, conf=0.78)

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Sorted by citations

Authors
Kietzmann, T.
Affiliations
University of Oulu (FI)
Corresponding author
Kietzmann, Thomas
ORCID
Kietzmann, Thomas
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2019-05-11
Volume
20
Issue
9
Pages
2347
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms20092347
PMC
PMC6540308
OpenAlex
W2944432144
Cited by
90
References
18
Citations by year
2026: 12 · 2025: 15 · 2024: 11 · 2023: 15 · 2022: 6 · 2021: 14 · 2020: 10 · 2019: 6
FWCI
1.18
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Suomalainen Tiedeakatemia (SA 296027)
  • Jane ja Aatos Erkon Säätiö (2015)
  • Sigrid Juséliuksen Säätiö (2019)
  • Lounais-Suomen Syöpäyhdistys (2018)
  • European Cooperation in Science and Technology (BM1203/EU‐ROS)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
liver zonation, hypoxia, hypoxia-inducible factor, oxygen gradients, β-catenin signaling, Hedgehog signaling, Hippo signaling pathway, liver disease, systemic homeostasis, metabolic zonation
MeSH terms
Animals, Hypoxia, Humans, Liver, Liver Diseases, Oxidation-Reduction, Oxygen, Transcription Factors

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