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dc.contributor.authorMcCracken, Jennifer M.
dc.contributor.authorJiang, Lu
dc.contributor.authorDeshpande, Krutika T.
dc.contributor.authorO'Neil, Maura F.
dc.contributor.authorPritchard, Michele T.
dc.date.accessioned2017-09-08T15:54:14Z
dc.date.available2017-09-08T15:54:14Z
dc.date.issued2016-03
dc.identifier.citationMcCracken, J. M., Jiang, L., Deshpande, K. T., O’Neil, M. F., & Pritchard, M. T. (2016). Differential effects of hyaluronan synthase 3 deficiency after acute vs chronic liver injury in mice. Fibrogenesis & Tissue Repair, 9, 4. http://doi.org/10.1186/s13069-016-0041-5en_US
dc.identifier.urihttp://hdl.handle.net/1808/24927
dc.descriptionA grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.en_US
dc.description.abstractBackground Hyaluronan (HA) is a ubiquitous extracellular matrix (ECM) glycosaminoglycan synthesized by three different enzymes, hyaluronan synthase (HAS)1, 2, and 3. HA synthesis mediated by HAS3 promotes inflammation and is pathogenic in animal models of human lung and intestinal disease. Liver fibrosis is a common endpoint to chronic liver injury and inflammation for which there is no cure. Although plasma HA is a commonly used biomarker for liver disease, if and how HA contributes to disease pathogenesis remains unclear. Here, we tested the hypothesis that HA synthesized by HAS3 enhances inflammation and fibrosis. To test this hypothesis, we exposed wild-type or Has3−/− mice to carbon tetrachloride (CCl4) once (acute) or ten (chronic) times.

Results HAS3-deficient mice exhibited increased hepatic injury and inflammatory chemokine production 48 h after acute CCl4; this was associated with a threefold reduction in plasma HA levels and alterations in the proportions of specific molecular weight HA polymer pools. Hepatic accumulation of fibrosis-associated transcripts was also greater in livers from HAS3-deficient mice compared to controls after acute CCl4 exposure. Surprisingly, fibrosis was not different between genotypes. Hepatic matrix metalloproteinase (MMP)13 mRNA and MMP13 activity was greater in livers from Has3-null mice after chronic CCl4; this was prevented by a MMP13-specific inhibitor. Collectively, these data suggest that Has3, or more likely HA produced by HAS3, limits hepatic inflammation after acute injury and attenuates MMP13-mediated matrix metabolism after chronic injury.

Conclusions These data suggest that HA should be investigated further as a novel therapeutic target for acute and chronic liver disease.

Electronic supplementary material The online version of this article (doi:10.1186/s13069-016-0041-5) contains supplementary material, which is available to authorized users.
en_US
dc.publisherBioMed Centralen_US
dc.rights© 2016 McCracken et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectFibrosisen_US
dc.subjectHyaluronanen_US
dc.subjectInflammationen_US
dc.subjectLiveren_US
dc.subjectMatrixen_US
dc.subjectMetalloproteinaseen_US
dc.titleDifferential effects of hyaluronan synthase 3 deficiency after acute vs chronic liver injury in miceen_US
dc.typeArticleen_US
kusw.kuauthorMcCracken, Jennifer M.
kusw.kuauthorJiang, Lu
kusw.kuauthorDeshpande, Krutika T.
kusw.kuauthorPritchard, Michele T.
kusw.kuauthorO'Neil, Maura F.
kusw.kudepartmentPharmacology, Toxicology and Therapeuticsen_US
kusw.kudepartmentPathologyen_US
dc.identifier.doi10.1186/s13069-016-0041-5en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmid4818527en_US
dc.rights.accessrightsopenAccess


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© 2016 McCracken et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Except where otherwise noted, this item's license is described as: © 2016 McCracken et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.