| Arch Otolaryngol Head Neck Surg. 1999 Nov;125(11):1239-43. |
|
Does cartilage down-regulate growth factor
expression in tracheal epithelium?
Hicks W Jr, Sigurdson
L, Gabalski E, Hard R, Hall L 3rd, Gardella
J, Powers C, Kumar N, Lwebuga-Mukasa J.
Department of Head and Neck Surgery, Roswell Park Cancer
Institute, Buffalo, NY 14263,
BACKGROUND: Maintaining tracheal integrity and restoring normal physiologic
function after injury is complex. Some of the critical events in this process
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
respiratory epithelial cells (REC) to migrate and
proliferate and restore denuded areas of the large conducting airway after
injury is poor. OBJECTIVE: To test the hypotheses that (1) the cartilaginous
framework, underlying the extracellular matrix (submucosa)
and epithelium, decreases the migratory ability of REC
when compared with REC on the same provisional extracellular
matrix (type I collagen) alone, and (2) this phenomenon is associated with
a change in expression of transforming growth factor (TGF)-alpha
and TGF-beta, both of which have been demonstrated
in cutaneous models to be 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 form cartilage, submucosa (type I collagen), and REC
(termed a "composite culture"). Control cultures consisted of epithelial
cells grown on type I collagen alone. Control and composite cultures were
evaluated morphologically using scanning electron and light microscopy. Expression
of TGF-alpha and TGF-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
less squamoid in morphological appearance than epithelial
cells on type I collagen alone. Expression of both growth factors was reduced
in epithelial cells 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.
PMID: 10555696 [PubMed
- indexed for MEDLINE]