Hyaluronan does not regulate human epidermal keratinocyte proliferation and differentiation

Jérémy Malaisse, Valérie Pendaries, Fanny Hontoir, Valérie De Glas, Daniel Van Vlaender, Michel Simon, Catherine Lambert de Rouvroit, Yves Poumay, Bruno Flamion

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs


Hyaluronan (HA) is synthesized by three HA synthases (HAS1, 2, and 3) and secreted in the extracellular matrix. In human skin, large amounts of HA are found in the dermis. HA is also synthesized by keratinocytes in the epidermis though its epidermal functions are not clearly identified yet. To investigate HA functions, we studied the effects of HA depletion on human keratinocyte physiology within in vitro reconstructed human epidermis. Inhibition of HA synthesis with 4-methylumbelliferone (4MU) did not modify the expression profile of the epidermal differentiation markers involucrin, keratin 10, and filaggrin during tissue reconstruction. In contrast, when keratinocytes were incubated with 4MU, cell proliferation was decreased. In an attempt to rescue the proliferation function, HA samples of various mean molecular masses were added to keratinocyte cultures treated with 4MU. These samples were unable to rescue the initial proliferation rate. Furthermore, treatments with HA-specific hyaluronidase, while removing almost all HA in keratinocyte cultures, did not alter the differentiation or proliferation processes. The differences between 4MU and hyaluronidase effects did not result from differences in intracellular HA, sulfated glycosaminoglycan concentration, apoptosis, or levels of HA receptors, all of which remained unchanged. Similarly, knockdown of UDP-glucose 6-dehydrogenase (UGDH) using lentiviral shRNA effectively decreased HA production but did not affect proliferation rate. Overall, these data suggest that HA levels in the human epidermis are not directly correlated with keratinocyte proliferation and differentiation and that incubation of cells with 4MU cannot equate with HA removal.

langue originaleAnglais
Pages (de - à)6347-6358
Nombre de pages18
journalThe Journal of Biological Chemistry
Numéro de publication12
Les DOIs
Etat de la publicationPublié - janv. 2016

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