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Spatially restricted hyaluronan production by Has2 drives epithelial tubulogenesis in vitro.

  • Soulié P Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland.
  • Chassot A Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland.
  • Ernandez T Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland.
  • Montesano R Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland.
  • Féraille E Department of Cell Physiology and Metabolism, University of Geneva Medical School, Geneva, Switzerland eric.feraille@unige.ch.
  • 2014-08-29
Published in:
  • American journal of physiology. Cell physiology. - 2014
3-D cell culture
epithelial morphogenesis
hyaluronan
tubulogenesis
Animals
Dogs
Enzyme Induction
Epithelial Cells
Glucuronosyltransferase
Hepatocyte Growth Factor
Humans
Hyaluronan Synthases
Hyaluronic Acid
MAP Kinase Signaling System
Madin Darby Canine Kidney Cells
Mice
Organogenesis
Transforming Growth Factor beta1
English 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.
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  • English
Open access status
green
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https://sonar.ch/global/documents/106377
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