Autophagic degradation of HAS2 in endothelial cells: A novel mechanism to regulate angiogenesis
Authors
Chen, Carolyn G.
Gubbiotti, Maria A.
Kapoor, Aastha
Han, Xiaorui
Yu, Yanglei
Linhardt, Robert J.
Iozzo, Renato V.
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2020-08-01
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
Autophagic 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.
Abstract
Hyaluronan 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.
Description
Matrix Biology, 90, 1-19
Note : 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.
Note : 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.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Matrix Biology
https://harc.rpi.edu/
Rensselaer Polytechnic Institute, Troy, NY
Matrix Biology
https://harc.rpi.edu/
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https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1016/j.matbio.2020.02.001