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Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism

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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.

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Acknowledgments

This work was supported by grants from the Canadian Institutes of Health Research (MP-89873), the Canadian Cancer Society Research Institute (#702828) and the Mizutani Foundation for Glycoscience to BTR. BC was supported by a joint studentship from the Manitoba Health Research Council and the Manitoba Institute of Child Health.

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Authors and Affiliations

  1. Departments of Biochemistry and Medical Genetics, University of Manitoba, 745 Bannatyne Ave, Winnipeg, MB, R3E 0J9, Canada

    Biswajit Chowdhury, Richard Hemming, Sana Faiyaz & Barbara Triggs-Raine

  2. 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

  3. Manitoba Institute of Child Health, 715 McDermot Ave, Winnipeg, MB, R3E 3P4, Canada

    Barbara Triggs-Raine

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  1. Biswajit Chowdhury
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Correspondence to Barbara Triggs-Raine.

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Chowdhury, B., Hemming, R., Faiyaz, S. et al. Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism. Histochem Cell Biol 145, 53–66 (2016). https://doi.org/10.1007/s00418-015-1373-8

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