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Xylosyltransferase 2 deficiency and organ homeostasis

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Abstract

In this paper we characterize the function of Xylosyltransferase 2 (XylT2) in different tissues to investigate the role XylT2 has in the proteoglycan (PG) biochemistry of multiple organs. The results show that in all organs examined there is a widespread and significant decrease in total XylT activity in Xylt2 knock out mice (Xylt2−/−). This decrease results in increased organ weight differences in lung, heart, and spleen. These findings, in addition to our previous findings of increased liver and kidney weight with loss of serum XylT activity, suggest systemic changes in organ function due to loss of XylT2 activity. The Xylt2−/− mice have splenomegaly due to enlargement of the red pulp area and enhanced pulmonary response to bacterial liposaccharide. Tissue glycosaminoglycan composition changes are also found. These results demonstrate a role of XylT2 activity in multiple organs and their PG content. Because the residual XylT activity in the Xylt2−/− is due to xylosyltransferase 1 (XylT1), these studies indicate that both XylT1 and XylT2 have important roles in PG biosynthesis and organ homeostasis.

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Abbreviations

CS:

Chondroitin sulfate

DMEM:

Dulbecco’s modified Eagle medium

ECM:

extracellular matrix

EDTA:

ethylenediaminetetracetic acid

FITC:

fluorescein isothiocyanate

GAG:

glycosaminoglycan

HP:

heparin sulfate

HS:

Heparan sulfate

LPS:

bacterial lipopolysaccharide

PAGE:

Polyacrylamide gel electrophoresis

PBS:

phosphate-buffered saline

PG:

proteoglycans

RBCs:

red blood cells

XylT2:

xylosyltransferase 2

XylT1:

xylosyltransferase 1

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Acknowledgements

This work was supported by Oklahoma Center for Advancement of Science and Technology, Oklahoma Center for Adult Stem Cell Research, and National Institutes of Health DK087989. We are thankful to the University of California at San Diego’s Glycoanalytics Core facility as well for expertise in disaccharide analyses. We are also very thankful for the helpful statistical advice of Ms. Binu Sharma.

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Authors and Affiliations

  1. Department of Physiological Sciences, Oklahoma State University, Stillwater, OK, 74078, USA

    Beatrix Ferencz, Eduard Condac, Nabin Poudel, Maria Cristina Munteanu, Pulavendran Sivasami, Melanie Breshears & Myron E. Hinsdale

  2. Glycotechnology Core Lab, Cellular and Molecular Medicine East, University of California, San Diego, La Jolla, CA, 92093-0687, USA

    Biswa Choudhury

  3. Waters Corporation, Stamford Avenue Altrincham Road, Wilmslow, SK9 4AX, UK

    Nandita Natasha Naidu

  4. Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180-3590, USA

    Fuming Zhang & Robert J. Linhardt

  5. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Myron E. Hinsdale

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  1. Beatrix Ferencz
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Correspondence to Myron E. Hinsdale.

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All mice were housed in facilities accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International: The Institutional Animal Care and Use Committees of all institutions approved all animal procedures and experiments.

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Ferencz, B., Condac, E., Poudel, N. et al. Xylosyltransferase 2 deficiency and organ homeostasis. Glycoconj J 37, 755–765 (2020). https://doi.org/10.1007/s10719-020-09945-9

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