title: Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism.
abstract: Hyaluronidase 2 (HYAL2) is a membrane-anchored protein that is proposed to initiate the degradation of hyaluronan (HA) in the extracellular matrix. The distribution of HYAL2 in tissues, and of HA in tissues lacking HYAL2, is largely unexplored despite the importance of HA metabolism in several disease processes. Herein, we use immunoblot and histochemical analyses to detect HYAL2 and HA in mouse tissues, as well as agarose gel electrophoresis to examine the size of HA. HYAL2 was detected in all tissues that were examined, including the brain. It was localized to the surface and cytoplasm of endothelial cells, as well as specialized epithelial cells in several tissues, including the skin. Accumulated HA, often of higher molecular mass than that in control tissues, was detected in tissues from Hyal2 (-/-) mice. The accumulating HA was located near to where HYAL2 is normally found, although in some tissues, it was distant from the site of HYAL2 localization. Overall, HYAL2 was highest in tissues that remove HA from the circulation (liver, lymph node and spleen), but the levels of HA accumulation in Hyal2 (-/-) mice were highest in tissues that catabolize locally synthesized HA. Our results support HYAL2's role as an extracellular enzyme that initiates HA breakdown in somatic tissues. However, our findings also suggest that HYAL2 contributes to HA degradation through other routes, perhaps as a soluble or secreted form.
authors.affiliation: Departments of Biochemistry and Medical Genetics, University of Manitoba, 745 Bannatyne Ave, Winnipeg, MB, R3E 0J9, Canada.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Chowdhury
authors.affiliation: Departments of Biochemistry and Medical Genetics, University of Manitoba, 745 Bannatyne Ave, Winnipeg, MB, R3E 0J9, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Hemming
authors.affiliation: Departments of Biochemistry and Medical Genetics, University of Manitoba, 745 Bannatyne Ave, Winnipeg, MB, R3E 0J9, Canada.
authors.forename: Sana
authors.initials: S
authors.lastname: Faiyaz
authors.affiliation: Departments of Biochemistry and Medical Genetics, University of Manitoba, 745 Bannatyne Ave, Winnipeg, MB, R3E 0J9, Canada. Barbara.Triggs-Raine@umanitoba.ca.|Pediatrics and Child Health, College of Medicine, Faculty of Health Sciences, University of Manitoba, 745 Bannatyne Ave, Winnipeg, MB, R3E 0J9, Canada. Barbara.Triggs-Raine@umanitoba.ca.|Manitoba Institute of Child Health, 715 McDermot Ave, Winnipeg, MB, R3E 3P4, Canada. Barbara.Triggs-Raine@umanitoba.ca.
authors.forename: Barbara
authors.identifier: http://orcid.org/0000-0003-4719-6779
authors.initials: B
authors.lastname: Triggs-Raine
mesh_terms: D000818:Animals; D004587:Electrophoresis, Agar Gel / Q000379:methods; D042783:Endothelial Cells / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics / Q000493:pharmacokinetics; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000096:biosynthesis* / Q000235:genetics / Q000493:pharmacokinetics*; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout
chemical_list: D058851:GPI-Linked Proteins; D006820:Hyaluronic Acid; C469221:Hyal2 protein, mouse; D006821:Hyaluronoglucosaminidase
keywords: Glycosaminoglycan; Hyaluronan; Hyaluronidase 2; Matrix degradation; Mouse model