Heparin interaction with a receptor on hyperglycemic dividing cells prevents intracellular hyaluronan synthesis and autophagy responses in models of type 1 diabetes

Aimin Wang; Nehru Viji Sankaranarayanan; Masaki Yanagishita; Douglas M Templeton; Umesh R Desai; Kazuyuki Sugahara; Christina P Wang; Vincent C Hascall

doi:10.1016/j.matbio.2015.04.003

Heparin interaction with a receptor on hyperglycemic dividing cells prevents intracellular hyaluronan synthesis and autophagy responses in models of type 1 diabetes

Matrix Biol. 2015 Oct:48:36-41. doi: 10.1016/j.matbio.2015.04.003. Epub 2015 Apr 16.

Authors

Aimin Wang¹, Nehru Viji Sankaranarayanan², Masaki Yanagishita³, Douglas M Templeton⁴, Umesh R Desai², Kazuyuki Sugahara⁵, Christina P Wang¹, Vincent C Hascall⁶

Affiliations

¹ Biomedical Engineering, Cleveland Clinic, Cleveland, OH, United States.
² Department of Medicinal Chemistry and Institute for Structural Biology, Virginia Commonwealth University, Richmond, VA, United States.
³ Division of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
⁵ Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
⁶ Biomedical Engineering, Cleveland Clinic, Cleveland, OH, United States. Electronic address: [email protected].

Abstract

Previous studies and ongoing research indicate the importance of an interaction between a putative receptor on dividing cells in hyperglycemia and the non-reducing end motifs of heparin stored in mast cell secretory granules and how this interaction prevents activation of hyaluronan synthesis in intracellular compartments and subsequent autophagy. This suggests a new role for endosomal heparanase in exposing this cryptic motif present in the initial large heparin chains on serglycin and in the highly sulfated (NS) domains of heparan sulfate.

Keywords: Heparan sulfate; Heparanase; Heparin; Heparitinase; Hyaluronan.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Animals
Autophagy / drug effects
Autophagy / genetics
Cell Division
Diabetes Mellitus, Experimental / drug therapy
Diabetes Mellitus, Experimental / genetics
Diabetes Mellitus, Experimental / metabolism*
Diabetes Mellitus, Experimental / pathology
Diabetes Mellitus, Type 1 / genetics
Diabetes Mellitus, Type 1 / metabolism
Diabetes Mellitus, Type 1 / pathology
Endosomes / drug effects
Endosomes / metabolism
Extracellular Matrix / chemistry
Extracellular Matrix / drug effects
Extracellular Matrix / metabolism
Gene Expression
Glucuronidase / genetics
Glucuronidase / metabolism*
Heparin / pharmacology*
Heparitin Sulfate / metabolism
Humans
Hyaluronic Acid / biosynthesis
Mast Cells / drug effects
Mast Cells / metabolism
Mast Cells / pathology
Mesangial Cells / drug effects
Mesangial Cells / metabolism*
Mesangial Cells / pathology
Proteoglycans / biosynthesis
Rats
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism*
Secretory Vesicles / chemistry
Secretory Vesicles / metabolism
Vesicular Transport Proteins / biosynthesis

Substances

Proteoglycans
Receptors, Cell Surface
Vesicular Transport Proteins
serglycin
Hyaluronic Acid
Heparin
Heparitin Sulfate
heparanase
Glucuronidase

Abstract

Publication types

MeSH terms

Substances

Grants and funding