TrkB is necessary for the normal development of the lung

• Published in: Respiratory physiology & neurobiology Vol. 167; no. 3; pp. 281 - 291
• Main Authors: García-Suárez, O, Pérez-Pinera, P, Laurà, R, Germana, A, Esteban, I, Cabo, R, Silos-Santiago, I, Cobo, J.L, Vega, J.A
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 31-07-2009; Elsevier
• Subjects: Animals; BDNF; Biological and medical sciences; Blotting, Western; Development; DNA - chemistry; DNA - genetics; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Lung; Lung - anatomy & histology; Lung - growth & development; Lung - ultrastructure; Medical Education; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron; Neurotrophin; Pulmonary/Respiratory; Receptor, trkB - genetics; Receptor, trkB - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - isolation & purification; TrkB; Vertebrates: respiratory system; Neurotrophin; Development; TrkB; BDNF; Lung; Vertebrata; Mammalia; trkB receptor; Brain derived neurotrophic factor; Respiratory system
• ISSN: 1569-9048; 1878-1519
• DOI: 10.1016/j.resp.2009.06.001

Abstract Normal development of the lung requires coordinated activation of cascades of signaling pathways initiated by growth factors signaling through their receptors. TrkB and its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4, belong to the neurotrophin family of growth factors, which are expressed in a large variety of non-neuronal tissues including the lung. Aberrant neurotrophin signaling underlies the pathogenesis of several lung-related pathologies, including asthma and lung cancer, however, little is known about the role of neurotrophins in the embryonic development of the lung. To fill this gap in knowledge, we analyzed the pattern of TrkB expression in the murine lung and we observed that TrkB is expressed in alveolar macrophages, type II pneumocytes, neuroepithelial bodies and nerves. Analysis of the structure of lung from mice deficient in TrkB revealed that absence of TrkB signaling results in thinner bronchial epithelium and apparent larger air space, and, more importantly, lack of neuroepithelial bodies, an important reduction in the density of nerve fibres in the bronchial smooth muscle, submucous plexus in bronchioles, and pulmonary artery walls. These findings suggest TrkB is essential for the normal development of the lung and the nervous system in the lung.