Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-10-28
pubmed:abstractText
Regenerative therapy of the salivary gland (SG) is a promising therapeutic approach for irreversible hyposalivation in patients with head and neck cancer treated by radiotherapy. However, little is known about the molecular regulators of stem/progenitor cell activity and regenerative processes in the SG. Wnt/?-catenin signaling regulates the function of many adult stem cell populations, but its role in SG development and regeneration is unknown. Using BAT-gal Wnt reporter transgenic mice, we demonstrate that in the submandibular glands (SMGs) of newborn mice Wnt/?-catenin signaling is active in a few cells at the basal layer of intercalated ducts, the putative location of salivary gland stem/progenitor cells (SGPCs). Wnt activity decreases as mice age, but is markedly enhanced in SG ducts during regeneration of adult SMG after ligation of the main secretory duct. The Hedgehog (Hh) pathway is also activated after duct ligation. Inhibition of epithelial ?-catenin signaling in young Keratin5-rtTA/tetO-Dkk1 mice impairs the postnatal development of SMG, particularly affecting maturation of granular convoluted tubules. Conversely, forced activation of epithelial ?-catenin signaling in adult Keratin5-rtTA/tetO-Cre/Ctnnb1((Ex3)fl) mice promotes proliferation of ductal cells, expansion of the SGPC compartment, and ectopic activation of Hh signaling. Taken together, these results indicate that Wnt/?-catenin signaling regulates the activity of SGPCs during postnatal development and regeneration upstream of the Hh pathway, and suggest the potential of modulating Wnt/?-catenin and/or Hh pathways for functional restoration of SGs after irradiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1557-8534
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1793-801
pubmed:dateRevised
2011-11-1
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Wnt/?-catenin signaling regulates postnatal development and regeneration of the salivary gland.
pubmed:affiliation
Molecular and Cellular Medicine Department, Institute for Regenerative Medicine at Scott & White, Texas A&M Health Science Center, Temple, Texas 76502, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural