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Cited by 535Liver physiology and pathologyLiver Diseases and ImmunityLiver Disease Diagnosis and Treatment

Origin of myofibroblasts in the fibrotic liver in mice

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Iwaisako, Keiko, Jiang, Chunyan, Zhang, Mingjun, Cong, Min, Moore-Morris, Thomas Joseph, Park, Tae Jun, Liu, Xiao, Xu, Jun +10 more·2014·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1400062111PMC PMC4136601
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Abstract

Significance: Liver resident activated hepatic stellate cells (aHSCs), and activated portal fibroblasts (aPFs) are the major source of the fibrous scar in the liver. aPFs have been implicated in liver fibrosis caused by cholestatic liver injury, whereas fibrosis in hepatotoxic liver injury is attributed to aHSCs. However, the contribution of aPFs to cholestatic fibrosis is not well characterized because of difficulties in cell purification and the lack of identified aPF-specific markers. We have developed a novel flow cytometry-based method of aPFs purification from the nonparenchymal cell fraction of collagen-α1(I)-GFP mice and have identified potential aPF-specific markers. The goal of this study is to determine whether aPFs contribute to cholestatic liver fibrosis and identify the mechanism(s) of their activation.

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  • Hepatic stellate cells are the predominant (>95%) source of collagen-producing cells and myofibroblasts in liver fibrosis.

    “hepatic stellate cells, the predominant (>95%) source of collagen-producing cells and myofibroblasts in liver fibrosis 15,43 .”

    From Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis (2024) · cites this paper as [43]

    The paper assigns the >95% figure to activated hepatic stellate cells and activated portal fibroblasts combined, not to stellate cells alone (opening summary; page unavailable). In “Activation of HSCs Differs in BDL- and CCl4-Induced Liver Injury” (page unavailable), stellate cells predominate after CCl4 injury but account for only 18 ± 7% of myofibroblasts at 5 days after bile duct ligation; portal fibroblasts predominate instead. (LLM, conf=0.90)

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References 79 · Cited by 535

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Authors
Iwaisako, K., Jiang, C., Zhang, M., Cong, M., Moore-Morris, T. J., Park, T. J., Liu, X., Xu, J., Wang, P., Paik, Y.-H., Meng, F., Asagiri, M., Murray, L. A., Hofmann, A. F., Iida, T., Glass, C. K., Brenner, D. A., & Kisseleva, T.
Affiliations
  • Kyoto University (JP)
  • Capital Medical University (CN)
  • Departments of aMedicine,
  • School of Pharmacy, University of California, San Diego, La Jolla, CA 92093;
  • Samsung Medical Center (KR)
  • Shandong University (CN)
  • MedImmune Ltd., Cambridge CB21 6GH, United Kingdom; and
  • Nihon University (JP)
  • Cellular and Molecular Medicine, and
  • Surgery, and
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2014-07-29
Volume
111
Issue
32
Pages
E3297-305
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1400062111
PMC
PMC4136601
OpenAlex
W1995212212
Cited by
535
References
79
Citations by year
2026: 24 · 2025: 34 · 2024: 55 · 2023: 53 · 2022: 53 · 2021: 49 · 2020: 59 · 2019: 39 · 2018: 39 · 2017: 45 · 2016: 43 · 2015: 33 · 2014: 8
FWCI
24.09
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • AJOU Open Repository (Ajou University) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • American Liver Foundation (DK72237, AA15055, GM41804)
  • National Institutes of Health (AA011999)
  • Japan Society for the Promotion of Science (24550107, 24689056, 24659822)
  • National Institute on Alcohol Abuse and Alcoholism (R01AA015055, AA15055, P50AA011999)
  • National Cancer Institute (P30CA023100)
  • National Institute of General Medical Sciences (GM41804, R01GM041804)
  • National Institute of Allergy and Infectious Diseases (AI0777802)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK72237, R01DK072237, P01DK074868, DK088837, R56DK088837, R01DK101737, R01DK099205)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
hepatic myofibroblasts, liver fibrosis, activated hepatic stellate cells, cholestatic liver injury, bile duct ligation, carbon tetrachloride hepatotoxicity, type I collagen, mesothelin, IL-25, IL-13, taurocholate, antifibrotic therapy
MeSH terms
Mesothelin, Collagen Type I, alpha 1 Chain, Animals, Carbon Tetrachloride, Cholestasis, Disease Models, Animal, Liver, Liver Cirrhosis, Mice, Inbred C57BL, Mice, Transgenic, Recombinant Proteins, Vitamin A, Collagen Type I, Green Fluorescent Proteins, Mice, Hepatic Stellate Cells, Chemical and Drug Induced Liver Injury, Myofibroblasts, GPI-Linked Proteins

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