title: Heparin interaction with a receptor on hyperglycemic dividing cells prevents intracellular hyaluronan synthesis and autophagy responses in models of type 1 diabetes.
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.
authors.affiliation: Biomedical Engineering, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: Aimin
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry and Institute for Structural Biology, Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Nehru Viji
authors.initials: NV
authors.lastname: Sankaranarayanan
authors.affiliation: Division of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yanagishita
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Templeton
authors.affiliation: Department of Medicinal Chemistry and Institute for Structural Biology, Virginia Commonwealth University, Richmond, VA, United States.
authors.forename: Umesh R
authors.initials: UR
authors.lastname: Desai
authors.affiliation: Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
authors.affiliation: Biomedical Engineering, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: Christina P
authors.initials: CP
authors.lastname: Wang
authors.affiliation: Biomedical Engineering, Cleveland Clinic, Cleveland, OH, United States. Electronic address: hascalv@ccf.org.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Hascall
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D002455:Cell Division; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D022142:Secretory Vesicles / Q000737:chemistry / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000096:biosynthesis; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006493:Heparin; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D033921:Vesicular Transport Proteins; D000099175:Heparanase; C075430:serglycin
keywords: Heparan sulfate; Heparanase; Heparin; Heparitinase; Hyaluronan