The Responses of Hyperglycemic Dividing Mesangial Cells to Heparin Are Mediated by the Non-reducing Terminal Trisaccharide

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2015

Erschienen:

2015

Enthalten in:

Zur Gesamtaufnahme - volume:290

Enthalten in:

The Journal of biological chemistry - 290(2015), 48 vom: 27. Nov., Seite 29045-50

Sprache:

Englisch

Beteiligte Personen:

Wang, Christina P [VerfasserIn]
Hascall, Vincent C [VerfasserIn]
Zhang, Fuming [VerfasserIn]
Linhardt, Robert J [VerfasserIn]
Abbadi, Amina [VerfasserIn]
Wang, Aimin [VerfasserIn]

Links:

Volltext

Themen:

9005-49-6
Diabetes
Diabetic nephropathy
Endoplasmic reticulum stress (ER stress)
Glucose metabolism
Heparanase
Heparin
Hyaluronan
Inflammation
Journal Article
Monocyte adhesive hyaluronan matrix
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Trisaccharide
Trisaccharides

Anmerkungen:

Date Completed 18.03.2016

Date Revised 05.02.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1074/jbc.M115.677401

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM252832604