Growth factors and fetal lung development mediated by mechanical forces

Figure 1 Mechanical forces generated by constant distension pressure (blue) and episodic breathing-like movements (red) are critical for normal fetal lung development.

Figure 2 Cyclic mechanical strain releases heparin binding epidermal growth factor-like growth factor and transforming growth factor alpha ligands. Fetal type II cells were transfected by electroporation with cDNA constructs encoding alkaline phosphatase-tagged heparin binding epidermal growth factor-like growth factor (HB-EGF) and transforming growth factor alpha (TGF-α) ligands. 24 h later, cells were exposed to 5% cyclic strain or 2.5% continuous strain for the indicated periods of time. Samples were processed to assess ligand-release into the supernatant using the alkaline phosphatase shedding assay protocol. Data are expressed as the intensity of each alkaline phosphatase (AP) supernatant band divided by total AP (supernatant + cell lysate). Upper panels shown representative blots. Data in the lower panels are from three independent experiments. ^aP < 0.05 vs unstretched samples for 1 h.

Figure 3 Mechanistic model. How mechanical forces promote differentiation of fetal type II epithelial cells via release of soluble growth factors heparin binding epidermal growth factor-like growth factor (HB-EGF) and transforming growth factor alpha (TGF-α) with subsequent binding and activation of the epidermal growth factor receptor and extracellular signal-regulated kinase (ERK) signaling pathway.