Xylosyltransferase 2 deficiency and organ homeostasis
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ORIGINAL ARTICLE
Xylosyltransferase 2 deficiency and organ homeostasis Beatrix Ferencz 1 & Eduard Condac 1 & Nabin Poudel 1 & Maria Cristina Munteanu 1 & Pulavendran Sivasami 1 & Biswa Choudhury 2 & Nandita Natasha Naidu 3 & Fuming Zhang 4 & Melanie Breshears 1 & Robert J. Linhardt 4 & Myron E. Hinsdale 1,5 Received: 13 January 2020 / Revised: 13 August 2020 / Accepted: 4 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Proteoglycans . Glycotransferase . Glycosaminoglycans . Extracellular matrix . Disaccharide analyses . Genetic modifier . Organ homeostasis . Proteoglycans . Xylosyltransferase
Introduction Proteoglycans (PGs) are found on the cell surface, in secretory granules, and in the extracellular matrix (ECM) [1]. At the cell surface, these biopolymers are fundamental to cellular processes including enhancement of receptor binding of cytokines and growth factors, and augmentation of enzymeElectronic supplementary material The online version of this article (https://doi.org/10.1007/s10719-020-09945-9) contains supplementary material, which is available to authorized users. * Myron E. Hinsdale [email protected] 1
Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA
2
Glycotechnology Core Lab, Cellular and Molecular Medicine East, University of California, San Diego, La Jolla, CA 92093-0687, USA
3
Waters Corporation, Stamford Avenue Altrincham Road, Wilmslow SK9 4AX, UK
4
Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA
5
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
substrate interactions important in coagulation and lipid catabolism [2–7]. In the ECM, PGs maintain basement membrane integrity, augment growth factor and cytokine sequestration, and create morphogen gradients [3, 8–10
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