TGFβ as a therapeutic target in cystic fibrosis

Introduction: Cystic fibrosis (CF) is a genetic disease characterized by progressive lung disease. Most CF therapies focus on treating secondary pulmonary complications rather than addressing the underlying processes inducing airway remodeling and ineffective response to infection. Transforming growth factor beta (TGF beta) is a cytokine involved in fibrosis, inflammation, and injury response as well as a genetic modifier and biomarker of CF lung disease. Targeting the TGF beta pathway has been pursued in other diseases, but the mechanism of TGF beta effects in CF is less well understood. Areas covered: In this review, we discuss CF lung disease pathogenesis with a focus on potential links to TGF beta. TGF beta signaling in lung health and disease is reviewed. Recent studies investigating TGF beta's impact in CF airway epithelial cells are highlighted. Finally, an overview of potential therapies to target TGF beta signaling relevant to CF are addressed. Expert opinion: The broad impact of TGF beta signaling on numerous cellular processes in homeostasis and disease is both a strength and a challenge to developing TGF beta dependent therapeutics in CF. We discuss the challenges inherent in developing TGF beta-targeted therapy, identifying appropriate patient populations, and questions regarding the timing of treatment. Future directions for research into TGF beta focused therapeutics are discussed.