@article{e613c4dae8ff4b68a59613c881d3665f,
title = "The abnormal accumulation of heparan sulfate in patients with mucopolysaccharidosis prevents the elastolytic activity of cathepsin V",
abstract = "Mucopolysaccharidosis (MPS) are rare inherited diseases characterized by accumulation of lysosomal glycosaminoglycans, including heparan sulfate (HS). Patients exhibit progressive multi-visceral dysfunction and shortened lifespan mainly due to a severe cardiac/respiratory decline. Cathepsin V (CatV) is a potent elastolytic protease implicated in extracellular matrix (ECM) remodeling. Whether CatV is inactivated by HS in lungs from MPS patients remained unknown. Herein, CatV colocalized with HS in MPS bronchial epithelial cells. HS level correlated positively with the severity of respiratory symptoms and negatively to the overall endopeptidase activity of cysteine cathepsins. HS bound tightly to CatV and impaired its activity. Withdrawal of HS by glycosidases preserved exogenous CatV activity, while addition of Surfen, a HS antagonist, restored elastolytic CatV-like activity in MPS samples. Our data suggest that the pathophysiological accumulation of HS may be deleterious for CatV-mediated ECM remodeling and for lung tissue homeostasis, thus contributing to respiratory disorders associated to MPS diseases.",
keywords = "Elastin, Glycosaminoglycan, Lung, MPS, Protease",
author = "Thibault Chazeirat and Sophie Denamur and Bojarski, {Krzysztof K.} and Andrault, {Pierre Marie} and Damien Sizaret and Fuming Zhang and Ahlame Saidi and Marine Tardieu and Linhardt, {Robert J.} and Fran{\c c}ois Labarthe and Dieter Br{\"o}mme and Samsonov, {Sergey A.} and Gilles Lalmanach and Fabien Lecaille",
note = "Funding Information: This work received funding from the French association Vaincre les Maladies Lysosomales (VML, Massy, France) and was supported by institutional fundings from the Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM), the University of Tours and GagoSciences (Structure, function and regulation of glycosaminoglycans; GDR 3739, Centre National de la Recherche Scientifique). TC holds a doctoral fellowship from MESRI (Minist{\`e}re de l'Enseignement Sup{\'e}rieur, de la Recherche et de l'Innovation, France). SD was supported by a French Pediatric Society (SFP) award. KKB holds a BMN (Badania M{\l}odych Naukowc{\'o}w) grant from the Faculty of Chemistry, University of Gda{\'n}sk (BMN-538-8370-B249-18) and a grant (UMO-2018/31/N/ST4/01677) from the National Science Centre of Poland (Narodowe Cenrtum Nauki). SS received funding (grant UMO-2018/30/E/ST4/00037) from the National Science Centre of Poland (Narodowe Centrum Nauki). We are grateful to Dr. Florian Mall{\`e}vre and Prof. Thierry Livache (Universit{\'e} Grenoble Alpes, CNRS, SPrAM, F-38000 Grenoble, France) for their excellent and skillful assistance in SPRi experiments. Authors acknowledge Prof. Laurent Duca (Universit{\'e} de Reims, Centre National de la Recherche Scientifique (CNRS) 7369, MEDyC, Reims, France) for providing purified bovine neck elastin, Dr. Romain Viv{\`e}s (Universit{\'e} de Grenoble Alpes, CNRS, Institut de Biologie Structurale, Grenoble, France) for providing the CHO cells, Dr. Michael McDermott (Department of Histopathology, Dublin, Ireland) for providing MPS type I lung tissue samples, and Prof. James McKerrow (Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego) for his gift of morpholinourea-leucinyl- homophenylalanine-vinyl-sulfone phenyl inhibitor (LHVS). Authors also acknowledge Dr Julie Chantreuil (Pediatric Intensive Care Unit, University Hospital of Tours, France) for her contribution to sample collection, and patients and their families enrolled in this study. Funding Information: This work received funding from the French association Vaincre les Maladies Lysosomales (VML, Massy, France) and was supported by institutional fundings from the Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM) , the University of Tours and GagoSciences (Structure, function and regulation of glycosaminoglycans ; GDR 3739 , Centre National de la Recherche Scientifique) . TC holds a doctoral fellowship from MESRI (Minist{\`e}re de l'Enseignement Sup{\'e}rieur, de la Recherche et de l'Innovation, France). SD was supported by a French Pediatric Society (SFP) award. KKB holds a BMN (Badania M{\l}odych Naukowc{\'o}w) grant from the Faculty of Chemistry, University of Gda{\'n}sk ( BMN-538-8370-B249-18 ) and a grant ( UMO-2018/31/N/ST4/01677 ) from the National Science Centre of Poland (Narodowe Cenrtum Nauki) . SS received funding (grant UMO- 2018/30/E/ST4/00037 ) from the National Science Centre of Poland (Narodowe Centrum Nauki) . We are grateful to Dr. Florian Mall{\`e}vre and Prof. Thierry Livache (Universit{\'e} Grenoble Alpes, CNRS, SPrAM, F-38000 Grenoble, France) for their excellent and skillful assistance in SPRi experiments. Authors acknowledge Prof. Laurent Duca (Universit{\'e} de Reims, Centre National de la Recherche Scientifique (CNRS) 7369, MEDyC, Reims, France) for providing purified bovine neck elastin, Dr. Romain Viv{\`e}s (Universit{\'e} de Grenoble Alpes, CNRS, Institut de Biologie Structurale, Grenoble, France) for providing the CHO cells, Dr. Michael McDermott (Department of Histopathology, Dublin, Ireland) for providing MPS type I lung tissue samples, and Prof. James McKerrow (Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego) for his gift of morpholinourea-leucinyl- homophenylalanine-vinyl-sulfone phenyl inhibitor (LHVS). Authors also acknowledge Dr Julie Chantreuil (Pediatric Intensive Care Unit, University Hospital of Tours, France) for her contribution to sample collection, and patients and their families enrolled in this study. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2021",
month = feb,
day = "1",
doi = "10.1016/j.carbpol.2020.117261",
language = "English",
volume = "253",
journal = "Carbohydrate Polymers",
issn = "0144-8617",
publisher = "Elsevier Ltd.",
}