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dc.contributor.authorChen, Carolyn G.
dc.contributor.authorGubbiotti, Maria A.
dc.contributor.authorKapoor, Aastha
dc.contributor.authorHan, Xiaorui
dc.contributor.authorYu, Yanglei
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorIozzo, Renato V.
dc.date2020
dc.date.accessioned2022-06-27T15:41:32Z
dc.date.available2022-06-27T15:41:32Z
dc.date.issued2020-08-01
dc.identifier.citationAutophagic degradation of HAS2 in endothelial cells: A novel mechanism to regulate angiogenesis, C. G. Chen, M. A. Gubbiotti, X. Han, Y. Yu, R. J. Linhardt, R. V. Iozzo, Matrix Biology, 90, 1-19, 2020.
dc.identifier.issn15691802
dc.identifier.issn0945053X
dc.identifier.urihttps://doi.org/10.1016/j.matbio.2020.02.001
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5497
dc.descriptionMatrix Biology, 90, 1-19
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractHyaluronan plays a key role in regulating inflammation and tumor angiogenesis. Of the three transmembrane hyaluronan synthases, HAS2 is the main pro-angiogenic enzyme responsible for excessive hyaluronan production. We discovered that HAS2 was degraded in vascular endothelial cells via autophagy evoked by nutrient deprivation, mTOR inhibition, or pro-autophagic proteoglycan fragments endorepellin and endostatin. Using live-cell and super-resolution confocal microscopy, we found that protracted autophagy evoked a dynamic interaction between HAS2 and ATG9A, a key transmembrane autophagic protein. This regulatory axis of HAS2 degradation occurred in various cell types and species and in vivo upon nutrient deprivation. Inhibiting in vivo autophagic flux via chloroquine showed increased levels of HAS2 in the heart and aorta. Functionally, autophagic induction via endorepellin or mTOR inhibition markedly suppressed extracellular hyaluronan production in vascular endothelial cells and inhibited ex vivo angiogenic sprouting. Thus, we propose autophagy as a novel catabolic mechanism regulating hyaluronan production in endothelial cells and demonstrate a new link between autophagy and angiogenesis that could lead to potential therapeutic modalities for angiogenesis.
dc.description.sponsorshipNational Institutes of Health
dc.description.urihttps://login.libproxy.rpi.edu/login?url=https://doi.org/10.1016/j.matbio.2020.02.001
dc.languageen_US
dc.language.isoENG
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofMatrix Biology
dc.relation.urihttps://harc.rpi.edu/
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleAutophagic degradation of HAS2 in endothelial cells: A novel mechanism to regulate angiogenesis
dc.typeArticle
dcterms.accessRightshttps://login.libproxy.rpi.edu/login?url=https://doi.org/10.1016/j.matbio.2020.02.001
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dcterms.isVersionOfhttps://doi.org/10.1016/j.matbio.2020.02.001
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.pages1-19
rpi.description.volume90


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