Table 1.

CF relevant effects and potential mechanisms of pathologic TGFβ actions in CF.

Effect	Suggested Mechanism	Relevance to CF	Refs
Downregulation of epithelial chloride transport	Downregulated CFTR and CaCC expression and function, potentially microRNA mediated	Exacerbates already dysregulated ion transport in epithelia throughout the body in CF	94, 95, 96
Driving goblet cell hyperplasia	Potentially via Smad dependent pathways based upon mouse models of allergen induced airway remodeling	Goblet cell hyperplasia and mucin secretion are pathologic features of CF lung disease	72, 73, 79
Aberrant inflammatory responses	Suppression of innate immune responses with augmented inflammation	CF lungs are known to be primed for a more aggressive inflammatory response, inability to clear chronic infection, and dysregulated innate immunity	104, 105, 106
Enhanced fibrosis	Driving myofibroblast differentiation and aberrant injury response that promotes fibrosis	After cycles of infection and inflammation, fibrotic lung disease significantly contributes to pulmonary decline in CF patients	56, 100, 101

CaCC, Calcium activated Chloride Conductance; CF, cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulation.