Does cartilage down-regulate growth factor expression in tracheal epithelium?

Background: Maintaining tracheal integrity and restoring normal physiologic function after injury is complex. Some of the critical events in this proc ess are deposition of a provisional extracellular matrix, tissue remodeling , and angiogenesis. These events are coordinated with epithelial migration and proliferation to restore the mucosal barrier. The ability of respirator y epithelial cells (REC) to migrate and proliferate and restore denuded are as of the large conducting airway after injury is poor. Objective: To test the hypotheses that(1) the cartilaginous framework, unde rlying the extracellular matrix (submucosa) and epithelium, decreases the m igratory ability of REC when compared with REC on the same provisional extr acellular matrix (type I collagen) alone, and (2) this phenomenon is associ ated with a change in expression of transforming growth factor (TGF)-alpha and TGF-beta, both of which have been demonstrated in cutaneous models to b e important in epithelial migration and proliferation. Design: We developed a culture system that reconstitutes the tracheal lumen in vitro, consisting of dissociated chondrocytes cultured in a manner to f orm cartilage, submucosa (type I collagen), and REC (termed a "composite cu lture"). Control cultures consisted of epithelial cells grown on type I col lagen alone. Control and composite cultures were evaluated morphologically using scanning electron and light microscopy. Expression of TGF-alpha and T GF-beta was determined in day 14 cultured epithelial cells from control and composite cultures by semiquantitative polymerase chain reaction. Results: Epithelial cells from composite cultures did not spread and were l ess squamoid in morphological appearance than epithelial cells on ripe I co llagen alone. Expression of both growth factors was reduced in epithelial c ells from composite cultures compared with those on type I collagen. Conclusions: Cartilage modulates TGF-alpha and TGF-beta expression in REC, and may contribute to regulation of REC proliferation and differentiation.