title: Spatially restricted hyaluronan production by Has2 drives epithelial tubulogenesis in vitro.
abstract: Generation of branched tubes from an epithelial bud is a fundamental process in development. We hypothesized that induction of hyaluronan synthase (Has) and production of hyaluronan (HA) drives tubulogenesis in response to morphogenetic cytokines. Treatment of J3B1A mammary cells with transforming growth factor-β1 or renal MDCK and mCCD-N21 cells with hepatocyte growth factor induced strong and specific expression of Has2. Immunostaining revealed that HA was preferentially produced at the tips of growing tubules. Inhibition of HA production, either by 4-methylumbelliferone (4-MU) or by Has2 mRNA silencing, abrogated tubule formation. HA production by J3B1A and mCCD-N21 cells was associated with sustained activation of ERK and S6 phosphorylation. However, silencing of either CD44 or RHAMM (receptor for HA-mediated motility), the major HA receptors, by RNA interference, did not alter tubulogenesis, suggesting that this process is not receptor-mediated.
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Soulié
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chassot
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernandez
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Montesano
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland eric.feraille@unige.ch.
authors.forename: Eric
authors.initials: E
authors.lastname: Féraille
mesh_terms: D000818:Animals; D004285:Dogs; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000201:enzymology; D014453:Glucuronosyltransferase / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D038081:Organogenesis; D053773:Transforming Growth Factor beta1 / Q000502:physiology
chemical_list: C066855:HGF protein, human; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C491099:Has2 protein, mouse; D000076002:Hyaluronan Synthases
keywords: 3-D cell culture; epithelial morphogenesis; hyaluronan; tubulogenesis