title: Parasympathetic stimulation improves epithelial organ regeneration.
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.
authors: Matrix and Morphogenesis Section, LCDB, NIDCR, NIH, 30 Convent Drive, Bethesda, Maryland 20892, USA.
authors: Sarah M
authors: SM
authors: Knox
authors: Isabelle M A
authors: IM
authors: Lombaert
authors: Candace L
authors: CL
authors: Haddox
authors: Shaun R
authors: SR
authors: Abrams
authors: Ana
authors: A
authors: Cotrim
authors: Adrian J
authors: AJ
authors: Wilson
authors: Matthew P
authors: MP
authors: Hoffman
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D004848:Epithelium / Q000254:growth & development / Q000294:innervation* / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D051101:Neurturin / Q000494:pharmacology; D038081:Organogenesis / Q000187:drug effects / Q000528:radiation effects; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D011839:Radiation, Ionizing; D012038:Regeneration / Q000187:drug effects / Q000528:radiation effects; D013363:Submandibular Gland / Q000187:drug effects / Q000294:innervation* / Q000502:physiology* / Q000528:radiation effects
chemical_list: D051101:Neurturin