title: Hyaluronidase 1 and hyaluronidase 2 are required for renal hyaluronan turnover.
abstract: Hyaluronidase 1 (HYAL1) and hyaluronidase 2 (HYAL2) are the major hyaluronidases acting synergistically to degrade hyaluronan (HA). In the kidney, HA is distributed heterogeneously. Our goal was to determine the consequences of a lack of either HYAL1 or HYAL2 (using specific knockout mice) on renal function and on renal HA accumulation. Experiments were performed in Hyal1(-/-) and Hyal2(-/-) mice and in their wild-type controls. HA concentration was measured in the plasma and kidney tissue and its distribution through the different kidney zones was examined by immunohistochemistry. Relative mRNA expressions of HYAL1, HYAL2 and the 3 main HA synthases were evaluated by quantitative RT-PCR. Results: Kidney function was not impaired in the knockout mice but they displayed elevated HA concentrations in the plasma and in the kidney. Hyal1(-/-) mice presented an accumulation of HA inside the proximal tubular cells whereas Hyal2(-/-) mice showed HA accumulation in the interstitial space. In the cortex and in the outer medulla, HYAL1 mRNA expression was up-regulated in Hyal2(-/-) mice. From our study we conclude that somatic hyaluronidases are not required for renal function. However, HYAL1 is necessary for the breakdown of intracellular HA in the cortex, whereas HYAL2 is essential for the degradation of extracellular HA in all kidney regions.
authors.affiliation: Molecular Physiology Research Unit (URPHYM)-NARILIS, University of Namur, Namur, Belgium. Electronic address: vanessa.colombaro@unamur.be.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Colombaro
authors.affiliation: Molecular Physiology Research Unit (URPHYM)-NARILIS, University of Namur, Namur, Belgium.
authors.forename: Inès
authors.initials: I
authors.lastname: Jadot
authors.affiliation: Molecular Physiology Research Unit (URPHYM)-NARILIS, University of Namur, Namur, Belgium; Laboratory of Experimental Nephrology, Université Libre de Bruxelles - ULB, Brussels, Belgium.
authors.forename: Anne-Emilie
authors.initials: AE
authors.lastname: Declèves
authors.affiliation: Molecular Physiology Research Unit (URPHYM)-NARILIS, University of Namur, Namur, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Voisin
authors.affiliation: Molecular Physiology Research Unit (URPHYM)-NARILIS, University of Namur, Namur, Belgium.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Giordano
authors.affiliation: Molecular Physiology Research Unit (URPHYM)-NARILIS, University of Namur, Namur, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Habsch
authors.affiliation: Molecular Physiology Research Unit (URPHYM)-NARILIS, University of Namur, Namur, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Flamion
authors.affiliation: Molecular Physiology Research Unit (URPHYM)-NARILIS, University of Namur, Namur, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Caron
mesh_terms: D000818:Animals; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000096:biosynthesis* / Q000235:genetics; D007672:Kidney Cortex / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D058851:GPI-Linked Proteins; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; C469220:Hyal1 protein, mouse; C469221:Hyal2 protein, mouse; D006821:Hyaluronoglucosaminidase
keywords: Hyaluronan; Hyaluronidases; Kidney