Similarly, much more pre-clinical research is necessary for determining the roles of individual PDE4 isoforms in critical aspects of the pathophysiology of pulmonary fibrosis, such as the migration, proliferation and differentiation of fibroblasts, the activation of the TGF-β pathway in these cells, and the role of fibroblasts in production and remodeling of the extracellular matrix. This evidence concerns the gene PDE4A and pulmonary fibrosis.