title: Hyaluronan and hyaluronan-binding proteins accumulate in both human type 1 diabetic islets and lymphoid tissues and associate with inflammatory cells in insulitis.
abstract: Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that is present in pancreatic islets, but little is known about its involvement in the development of human type 1 diabetes (T1D). We have evaluated whether pancreatic islets and lymphoid tissues of T1D and nondiabetic organ donors differ in the amount and distribution of HA and HA-binding proteins (hyaladherins), such as inter-α-inhibitor (IαI), versican, and tumor necrosis factor-stimulated gene-6 (TSG-6). HA was dramatically increased both within the islet and outside the islet endocrine cells, juxtaposed to islet microvessels in T1D. In addition, HA was prominent surrounding immune cells in areas of insulitis. IαI and versican were present in HA-rich areas of islets, and both molecules accumulated in diabetic islets and regions exhibiting insulitis. TSG-6 was observed within the islet endocrine cells and in inflammatory infiltrates. These patterns were only observed in tissues from younger donors with disease duration of <10 years. Furthermore, HA and IαI amassed in follicular germinal centers and in T-cell areas in lymph nodes and spleens in T1D patients compared with control subjects. Our observations highlight potential roles for HA and hyaladherins in the pathogenesis of diabetes.
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, WA.
authors.forename: Marika
authors.initials: M
authors.lastname: Bogdani
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, WA.
authors.forename: Pamela Y
authors.initials: PY
authors.lastname: Johnson
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, WA.
authors.forename: Susan
authors.initials: S
authors.lastname: Potter-Perigo
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, WA.
authors.forename: Nadine
authors.initials: N
authors.lastname: Nagy
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, U.K.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Day
authors.affiliation: Division of Infectious Diseases, Stanford University Medical Center, Stanford, CA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Bollyky
authors.affiliation: Matrix Biology Program, Benaroya Research Institute, Seattle, WA twight@benaroyaresearch.org.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D000510:Alpha-Globulins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D007223:Infant; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism*; D008875:Middle Aged; D053675:Versicans / Q000235:genetics / Q000378:metabolism
chemical_list: D000510:Alpha-Globulins; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; D007328:Insulin; C072273:TNFAIP6 protein, human; D053675:Versicans; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid