Parasympathetic stimulation improves epithelial organ regeneration

Sarah M. Knox, Isabelle M. A. Lombaert, Candace L. Haddox, Shaun R. Abrams, Ana Cotrim, Adrian J. Wilson and Matthew P. Hoffman ()
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Sarah M. Knox: Matrix and Morphogenesis Section, LCDB, NIDCR, NIH
Isabelle M. A. Lombaert: Matrix and Morphogenesis Section, LCDB, NIDCR, NIH
Candace L. Haddox: Matrix and Morphogenesis Section, LCDB, NIDCR, NIH
Shaun R. Abrams: Matrix and Morphogenesis Section, LCDB, NIDCR, NIH
Ana Cotrim: Molecular Physiology and Therapeutics Branch, NIDCR, NIH
Adrian J. Wilson: Matrix and Morphogenesis Section, LCDB, NIDCR, NIH
Matthew P. Hoffman: Matrix and Morphogenesis Section, LCDB, NIDCR, NIH

Nature Communications, 2013, vol. 4, issue 1, 1-7

Abstract: Abstract Parasympathetic nerves are a vital component of the progenitor cell niche during development, maintaining a pool of progenitors for organogenesis. Injured adult organs do not regenerate after parasympathectomy, and there are few treatments to improve organ regeneration, particularly after damage by therapeutic irradiation. Here we show that restoring parasympathetic function with the neurotrophic factor neurturin increases epithelial organ regeneration after damage. We use mouse salivary gland explant culture containing fluorescently labelled progenitors, and injure the tissue with irradiation. The progenitors survive, parasympathetic function is diminished and epithelial apoptosis reduces the expression of neurturin, which increases neuronal apoptosis. Treatment with neurturin reduces neuronal apoptosis, restores parasympathetic function and increases epithelial regeneration. Furthermore, adult human salivary glands damaged by irradiation also have reduced parasympathetic innervation. We propose that neurturin will protect the parasympathetic nerves from damage and improve organ regeneration. This concept may be applicable for other organs where parasympathetic innervation influences their function.

Date: 2013
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DOI: 10.1038/ncomms2493

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