Autophagic degradation of HAS2 in endothelial cells: A novel mechanism to regulate angiogenesis
No Thumbnail Available
Authors
Chen, Carolyn G.
Gubbiotti, Maria A.
Kapoor, Aastha
Han, Xiaorui
Yu, Yanglei
Linhardt, Robert J.
Iozzo, Renato V.
Issue Date
2020-08-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
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.
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.
Publisher
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
15691802
0945053X
0945053X