Adult primary lung cells were isolated as described in [37] with small modifications. Briefly, lungs were isolated, cut in small pieces and digested over-night at 4uC with 0.1% protease type-XIV (Sigma-Aldrich, P5149) in Joklik's MEM (Sigma Aldrich, 8028) containing antibiotics (Gibco, 15070). Lung pieces were transferred in Joklik's MEM supplemented with 10% FBS (Gibco 10500), pipetted gently several times to release cells and passed through 70 mm cell strainer (BD Biosciences, 352350). Cells were washed with MCDB-201 (Sigma-Aldrich, M6770) containing Insulin-Transferrin-Selenium (Gibco, 51300-044) and viability was measured using Trypan Blue. 10 6 cells (10 6 /ml) were cultured in 12-well plates (Nunc, 150628) coated with Bovine collagen (Nutacon, 5409) for 24 hours. Coating was done with 100 mg/cm 2 collagen, for 1 hour at 37uC. Thereafter, cultures were rinsed with MCDB-201 to remove detached cells and 500 ml MCDB-201 with Insulin-Transferrin-Selenium and 1 ng/ml EGF (Peprotech, 315-09) was added. After 1 week, colonies of epithelial cells were formed and infected with recombinant adenoviruses expressing either constitutively-activated ALK3 (caALK3), caALK5, Smad1 or Smad3. After 48 hours incubation the treated cells were used either for cytochemistry or for RNA extraction.