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The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue‐Specific Perspectives

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Title: The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue‐Specific Perspectives
Authors: Vahdatahar, Elham, Daviaud, Clément, Main, Hugo, Havret, Rachel, Debarnot, Claire, Favot-Laforge, Laure, Jégou, Jean‐François, Fruitier-Arnaudin, Ingrid, Dufour, Antoine, Vivès, Romain, Morel, Franck, Bourne, Yves, Baranger, Kévin
Contributors: Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LIttoral ENvironnement et Sociétés (LIENSs), Institut national des sciences de l'Univers (INSU - CNRS)-La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Laboratoire inflammation, tissus épithéliaux et cytokines UR 15560 (LITEC Poitiers ), Université de Poitiers = University of Poitiers (UP), University of Calgary, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Ligue Contre le Cancer (French League Against Cancer), La Rochelle Université (ULR), Conseil Régional Aquitaine (Région Nouvelle-Aquitaine), Université de Poitiers (UP), Aix-Marseille Université (AMU), Canadian Government, ANR-21-CE44-0004,HeparInfSkin,Décrypter les mécanismes inflammatoires induits par l'activité enzymatique de l'héparanase dans les maladies de la peau en utilisant un inhibiteur naturel dérivé d'un polysaccharide marin(2021), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-15-IDEX-0002,UGA,IDEX UGA(2015), ANR-21-CE29-0022,CarboCHIPS,Des biopuces pour l'étude des séquences saccharidiques au sein d'assemblages supramoléculaires par spectrométrie de masse(2021), ANR-22-CE15-0041,NEUTROGAG,Les glycosaminoglycanes du neutrophile: diversité et fonctions(2022)
Source: ISSN: 0892-6638.
Publisher Information: CCSD
Federation of American Society of Experimental Biology
Publication Year: 2025
Collection: Aix-Marseille Université: HAL
Subject Terms: Cancer, Heparanase, Immune cell, Molecular modeling, Mouse model, Skin inflammation, MESH: Animals, MESH: Evolution, Molecular, MESH: Glucuronidase* / chemistry, MESH: Glucuronidase* / genetics, MESH: Glucuronidase* / metabolism, MESH: Heparitin Sulfate / metabolism, MESH: Humans, MESH: Mice, MESH: Neoplasms / enzymology, [SDV]Life Sciences [q-bio]
Description: International audience ; Heparanase 1 (HPSE1) is a unique endoglycosidase responsible for the enzymatic cleavage of heparan sulfate, thereby playing important functions in cancer processes. In contrast, the structurally related Heparanase 2 (HPSE2) lacks catalytic activity and appears to counteract HPSE1 activities. However, contradictory observations in various pathologies highlight the need for a better understanding of the respective contributions of both heparanases. In this review, we provide a comprehensive resource about the biology of HPSE1 and HPSE2 based on findings from different mouse models, with an emphasis on immune cells and their involvement in skin pathophysiology. In addition, we explore the evolutionary relationships between the two heparanases and describe the structure–function of HPSE2 using the advanced protein‐prediction tool AlphaFold 3 (AF3). These approaches unveil new insights for deciphering the functional molecular determinants that distinguish HPSE1 from HPSE2.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/40899692; PUBMED: 40899692; PUBMEDCENTRAL: PMC12406646; WOS: 001563883000001
DOI: 10.1096/fj.202501859R
Availability: https://hal.science/hal-05251863
https://hal.science/hal-05251863v1/document
https://hal.science/hal-05251863v1/file/The%20FASEB%20Journal%20-%202025%20-%20Vahdatahar%20-%20The%20Pathophysiological%20Functions%20of%20Heparanases%20From%20Evolution%20Structural%20and.pdf
https://doi.org/10.1096/fj.202501859R
Rights: http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.C0256949
Database: BASE
Description
Abstract:International audience ; Heparanase 1 (HPSE1) is a unique endoglycosidase responsible for the enzymatic cleavage of heparan sulfate, thereby playing important functions in cancer processes. In contrast, the structurally related Heparanase 2 (HPSE2) lacks catalytic activity and appears to counteract HPSE1 activities. However, contradictory observations in various pathologies highlight the need for a better understanding of the respective contributions of both heparanases. In this review, we provide a comprehensive resource about the biology of HPSE1 and HPSE2 based on findings from different mouse models, with an emphasis on immune cells and their involvement in skin pathophysiology. In addition, we explore the evolutionary relationships between the two heparanases and describe the structure–function of HPSE2 using the advanced protein‐prediction tool AlphaFold 3 (AF3). These approaches unveil new insights for deciphering the functional molecular determinants that distinguish HPSE1 from HPSE2.
DOI:10.1096/fj.202501859R