title: Hyaluronan metabolism in human keratinocytes and atopic dermatitis skin is driven by a balance of hyaluronan synthases 1 and 3.
abstract: Hyaluronan (HA) is a glycosaminoglycan synthesized directly into the extracellular matrix by three hyaluronan synthases (HAS1, HAS2, and HAS3). HA is abundantly synthesized by keratinocytes but its epidermal functions remain unclear. We used culture models to grow human keratinocytes as autocrine monolayers or as reconstructed human epidermis (RHE) to assess HA synthesis and HAS expression levels during the course of keratinocyte differentiation. In both the models, epidermal differentiation downregulates HAS3 mRNA expression while increasing HAS1 without significant changes in hyaluronidase expression. HA production correlates with HAS1 mRNA expression level during normal differentiation. To investigate the regulation of HAS gene expression during inflammatory conditions linked to perturbed differentiation, lesional and non-lesional skin biopsies of atopic dermatitis (AD) patients were analyzed. HAS3 mRNA expression level increases in AD lesions compared with healthy and non-lesional skin. Simultaneously, HAS1 expression decreases. Heparin-binding EGF-like growth factor (HB-EGF) is upregulated in AD epidermis. An AD-like HAS expression pattern is observed in RHE incubated with HB-EGF. These results indicate that HAS1 is the main enzyme responsible for HA production by normal keratinocytes and thus, must be considered as an actor of normal keratinocyte differentiation. In contrast, HAS3 can be induced by HB-EGF and seems mainly involved in AD epidermis.
authors.affiliation: Research Unit of Molecular Physiology (URPHYM), NARILIS, University of Namur, Namur, Belgium.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Malaisse
authors.affiliation: Research Unit of Molecular Physiology (URPHYM), NARILIS, University of Namur, Namur, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bourguignon
authors.affiliation: Research Unit of Molecular Physiology (URPHYM), NARILIS, University of Namur, Namur, Belgium.
authors.forename: Evelyne
authors.initials: E
authors.lastname: De Vuyst
authors.affiliation: Research Unit of Molecular Physiology (URPHYM), NARILIS, University of Namur, Namur, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lambert de Rouvroit
authors.affiliation: Department of Dermatology, University Medical Center of Liège, Liège, Belgium.
authors.forename: Arjen F
authors.initials: AF
authors.lastname: Nikkels
authors.affiliation: Research Unit of Molecular Physiology (URPHYM), NARILIS, University of Namur, Namur, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Flamion
authors.affiliation: Research Unit of Molecular Physiology (URPHYM), NARILIS, University of Namur, Namur, Belgium. Electronic address: yves.poumay@unamur.be.
authors.forename: Yves
authors.initials: Y
authors.lastname: Poumay
mesh_terms: D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000502:physiology*; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
chemical_list: D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C523794:HAS1 protein, human; C105458:HAS3 protein, human; D000076002:Hyaluronan Synthases; D066246:ErbB Receptors