Hyaluronan and Hyaluronan Binding Proteins Accumulate in both Human Type 1 Diabetic Islets and Lymphoid Tissues and Associate with Inflammatory Cells in Insulitis

  1. Thomas N. Wight1
  1. 1Matrix Biology Program, Benaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101;
  2. 2Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, UK; and
  3. 3Division of Infectious Diseases, Stanford University Medical Center, Stanford, CA 94305.
  1. Corresponding Author: Thomas N. Wight, PhD, Email: twight{at}benaroyaresearch.org

Abstract

Hyaluronan 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 non-diabetic organ donors differ in the amount and distribution of hyaluronan and hyaluronan binding proteins (hyaladherins) such as inter-α-inhibitor (IαI), versican, and tumor necrosis factor-stimulated gene-6 (TSG-6). Hyaluronan was dramatically increased both within the islet and outside the islet endocrine cells, juxtaposed to islet microvessels in T1D. In addition, hyaluronan was prominent surrounding immune cells in areas of insulitis. IαI and versican were present in hyaluronan-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 less than 10 years. Furthermore, hyaluronan and IαI amassed in follicular germinal centers and in T-cell areas in lymph nodes and spleens in T1D compared to controls. Our observations highlight potential roles for hyaluronan and hyaladherins in the pathogenesis of diabetes.

  • Received November 1, 2013.
  • Accepted March 24, 2014.

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