Cited by 166Liver physiology and pathologyProteoglycans and glycosaminoglycans researchLiver Disease Diagnosis and Treatment

Hyaluronan synthase 2–mediated hyaluronan production mediates Notch1 activation and liver fibrosis

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Yang, Yoon Mee, Noureddin, Mazen, Liu, Cheng, Ohashi, Koichiro, Kim, So Yeon, Ramnath, Divya, Powell, Elizabeth E., Sweet, Matthew J. +12 more·2019·Science Translational Medicine

Abstract

Hepatic stellate cells activated by hyaluronan synthase 2–mediated hyaluronan and Notch1 promote liver fibrosis, identifying a potential target.

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Crossref · 10.1126/scitranslmed.aat9284

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  • HSCs synthesize hyaluronic acid via HAS2, which promotes fibrogenicity in a NOTCH1-dependent manner by stimulating TLR4 and CD44 on HSCs.

    “Furthermore, HSCs synthesize hyaluronic acid through the expression of hyaluronic acid synthase 2, which promotes fibrogenicity in a NOTCH1-dependent manner by stimulating TLR4 and CD44 expressed on HSCs themselves (154).”

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Authors
Yang, Y. M., Noureddin, M., Liu, C., Ohashi, K., Kim, S. Y., Ramnath, D., Powell, E. E., Sweet, M. J., Roh, Y. S., Hsin, I.-F., Deng, N., Liu, Z., Liang, J., Mena, E., Shouhed, D., Schwabe, R. F., Jiang, D., Lu, S. C., Noble, P. W., & Seki, E.
Affiliations
  • Cedars-Sinai Medical Center (US)
  • Shanghai University of Traditional Chinese Medicine (CN)
  • The University of Queensland (AU)
  • California Liver Research Institute (US)
  • Columbia University (US)
Corresponding author
  • Noureddin, Mazen
  • Liu, Cheng
  • Seki, Ekihiro
Venue
Science Translational Medicine
Published
2019-06-12
Volume
11
Issue
496
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
OpenAlex
W2952382623
Cited by
166
References
52
Citations by year
2026: 13 · 2025: 32 · 2024: 28 · 2023: 30 · 2022: 19 · 2021: 25 · 2020: 14 · 2019: 5
FWCI
10.04
Type
journal article
Language
en
Open access
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute on Alcohol Abuse and Alcoholism (R21AA025841, R01 AA027036)
  • National Heart, Lung, and Blood Institute (R01HL122068, 1T32HL134637-01, P01HL108793)
  • National Institute of Allergy and Infectious Diseases (R01AI052201)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK085252, R01DK107288)
  • American Liver Foundation (ALF Irwin M. Arias, MD Postdoctoral Research Fellowship, ALF Congressman John Joseph Moakley Postdoctoral Research Fellowship)
  • American Association for the Study of Liver Diseases (AASLD The Leonard B. Seeff Award for Outstanding Research by Young Investigator)
  • Cedars-Sinai Medical Center (Winnick Research award)
  • Kangwon National University
  • National Research Foundation of Korea (2014R1A6A3A01054056, 2017R1A5A2015541, 2017R1C1B2004423)
  • Colleges and universities in Shanghai (A-U151902)
  • National Natural Science Foundation of China (81673788)
  • National Health and Medical Research Council of Australia (NHMRC Senior Research Fellowship, ID: 1107914)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
hyaluronic acid, HAS2, liver fibrosis, Notch1, hepatic stellate cells, stellate cell activation, TGF-beta, Wilms tumor 1, CD44, TLR4, 4-methylumbelliferone, extracellular matrix, fibrosis treatment
MeSH terms
Hyaluronan Synthases, RNA-Seq, Enzyme-Linked Immunosorbent Assay, Humans, Hyaluronic Acid, Hymecromone, Liver Cirrhosis, Hyaluronan Receptors, Toll-Like Receptor 4, Hepatic Stellate Cells, HEK293 Cells

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