Neurotrophin Regulation and Signaling in Airway Smooth Muscle

Structural and functional aspects of bronchial airways are key throughout life and play critical roles in diseases such as asthma. Asthma involves functional changes such as airway irritability and hyperreactivity, as well as structural changes such as enhanced cellular proliferation of airway smooth muscle (ASM), epithelium, and fibroblasts, and altered extracellular matrix (ECM) and fibrosis, all modulated by factors such as inflammation. There is now increasing recognition that disease maintenance following initial triggers involves a prominent role for resident nonimmune airway cells that secrete growth factors with pleiotropic autocrine and paracrine effects. The family of neurotrophins may be particularly relevant in this regard. Long recognized in the nervous system, classical neurotrophins such as brain-derived neurotrophic factor (BDNF) and nonclassical ligands such as glial-derived neurotrophic factor (GDNF) are now known to be expressed and functional in non-neuronal systems including lung. However, the sources, targets, regulation, and downstream effects are still under investigation. In this chapter, we discuss current state of knowledge and future directions regarding BDNF and GDNF in airway physiology and on pathophysiological contributions in asthma.