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Spatially restricted hyaluronan production by Has2 drives epithelial tubulogenesis in vitro

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Published in American Journal of Physiology. Cell Physiology. 2014, vol. 307, no. 8, p. C745-59
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.
Keywords AnimalsDogsEnzyme InductionEpithelial Cells/enzymologyGlucuronosyltransferase/physiologyHepatocyte Growth Factor/physiologyHumansHyaluronic Acid/biosynthesisMAP Kinase Signaling SystemMadin Darby Canine Kidney CellsMiceOrganogenesisTransforming Growth Factor beta1/physiology
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PMID: 25163516
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SOULIE, Priscilla et al. Spatially restricted hyaluronan production by Has2 drives epithelial tubulogenesis in vitro. In: American Journal of Physiology. Cell Physiology, 2014, vol. 307, n° 8, p. C745-59. https://archive-ouverte.unige.ch/unige:74280

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Deposited on : 2015-07-22

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