The responses of hyperglycemic dividing mesangial cells to heparin is mediated by the non-reducing terminal trisaccharide

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Authors
Wang, Christina P.
Hascall, Vincent C.
Zhang, Fuming
Linhardt, Robert J.
Abbadi, Amina
Wang, Aimin
Issue Date
2015-11-27
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
Our previous studies showed: (i) that growth-arrested G0/G1 rat mesangial cells stimulated to divide in hyperglycemic medium initiate intracellular hyaluronan synthesis that induces autophagy and the cyclin D3-induced formation of a monocyte-adhesive extracellular hyaluronan matrix after completing cell division; and (ii) that heparin inhibits the intracellular hyaluronan and autophagy responses, but after completing division, induces hyaluronan synthesis at the plasma membrane with the formation of a larger monocyte-adhesive hyaluronan matrix. This study shows: (i) that the non-terminal trisaccharide of heparin is sufficient to initiate the same responses as intact heparin, (ii) that a fully sulfated tetrasaccharide isolated from bacterial heparin lyase 1 digests of heparin that contains a Δ-2S-iduronate on the non-reducing end does not initiate the same responses as intact heparin, and (iii) that removal of the Δ-2S-iduronate to expose the fully sulfated trisaccharide (GlcNS(6S)-IdoUA(2S)-GlcNS(6S)) does initiate the same responses as intact heparin. These results provide evidence that mammalian heparanase digestion of heparin and heparan sulfate exposes a cryptic motif on the non-reducing termini that is recognized by a receptor on dividing cells.
Description
Journal of Biological Chemistry, 290, 29045–29050
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Full Citation
The responses of hyperglycemic dividing mesangial cells to heparin is mediated by the non-reducing terminal trisaccharide. C.P. Wang, V.C. Hascall, F. Zhang, R.J. Linhardt, A. Abbadi, A Wang, Journal of Biological Chemistry, 290, 29045–29050, 2015.
Publisher
American Society for Biochemistry and Molecular Biology (ASBMB) and Elsevier
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DOI
ISSN
1083351X
219258
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