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(American Journal of Pathology. 1999;155:1183-1193.)
© 1999 American Society for Investigative Pathology


Regular Articles

Abundant Production of Brain-Derived Neurotrophic Factor by Adult Visceral Epithelia

Implications for Paracrine and Target-Derived NeurotrophicFunctions

Marek Lommatzsch*, Armin Braun*, Anne Mannsfeldt{ddagger}, Vladimir A. Botchkarev{dagger}, Natalia V. Botchkareva{dagger}, Ralf Paus, Axel Fischer§, Gary R. Lewin{ddagger} and Harald Renz*

From the Departments of Laboratory Medicine and Pathobiochemistry *
and Dermatology,{dagger}
Charité, Humboldt University, Berlin; the Growth Factor and Regeneration Group,{ddagger}
Max Delbrück Centrum (MDC) for Molecular Medicine, Berlin; and the Department of Anatomy and Cell Biology,§
Justus Liebig University, Giessen, Germany; and the Department of Dermatology,
University Hospital, Eppendorf University, Hamburg, Germany

Brain-derived neurotrophic factor (BDNF) plays a crucial role for the survival of visceral sensory neurons during development. However, the physiological sources and the function of BDNF in the adult viscera are poorly described. We have investigated the cellular sources and the potential role of BDNF in adult murine viscera. We found markedly different amounts of BDNF protein in different organs. Surprisingly, BDNF levels in the urinary bladder, lung, and colon were higher than those found in the brain or skin. In situ hybridization experiments revealed that BDNF mRNA was made by visceral epithelial cells, several types of smooth muscle, and neurons of the myenteric plexus. Epithelia that expressed BDNF lacked both the high- and low-affinity receptors for BDNF, trkB and p75NTR. In contrast, both receptors were present on neurons of the peripheral nervous system. Studies with BDNF-/-mice demonstrated that epithelial and smooth muscle cells developed normally in the absence of BDNF. These data provide evidence that visceral epithelia are a major source, but not a target, of BDNF in the adult viscera. The abundance of BDNF protein in certain internal organs suggests that this neurotrophin may regulate the function of adult visceral sensory and motor neurons.





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