Functional Restoration of Salivary Glands After Radiotherapy: Roles of Wnt and Hedgehog Pathways
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Many head and neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, which significantly compromises their quality of life. This condition is caused by lack of regeneration following radiation damage due to loss of functional stem/progenitor cells and deterioration of the microenvironment. Current treatments such as artificial saliva and saliva secretion stimulators can only temporarily relieve the symptoms. Wnt and Hedgehog intercellular pathways are highly conserved during evolution and regulates regeneration or repair of various tissues after injury. We found recently that both Wnt and Hedgehog signalling activities are marginal in adult salivary gland but significantly upregulated during their functional regeneration after physical injury and promote expansion of salivary stem/progenitor cells, while radiation does not activate Wnt pathway in salivary gland. Transient activation of Wnt pathway prevented radiation-induced hyposalivation through inhibition of apoptosis and maintenance of salivary stem/progenitor cell populations.
