Transforming growth factor-beta1, myofibroblasts, and tissue remodeling in the pathogenesis of tracheal injury: potential role of gastroesophageal reflux.
Subglottic stenosis (SGS) is characterized by the obliteration of the tracheal lumen due to excessive deposition of connective tissue. We hypothesize that tracheal injury triggers the early production of transforming growth factor-beta1 (TGF-beta1), a factor implicated in fibroproliferative disorders. In turn, TGF-beta1 stimulates the transformation of tracheal fibroblasts into myofibroblasts with increased matrix production and scar contraction that might be influential in laying the foundation for the development of SGS. Consistent with this hypothesis, histologic analysis of tracheas from humans with SGS and from rats with experimental tracheal injury revealed increased alpha-smooth muscle actin-positive cells as compared to control tracheas, suggesting increased myofibroblast differentiation. Rat tracheal fibroblasts exposed to TGF-beta1 or gastric juice in vitro showed increased expression of alpha-smooth muscle actin, alterations in the expression of matrix molecules, and increased contraction of collagen gels. These findings suggest that gastric juice or other agents of tracheal injury promote tissue remodeling through the stimulation of the differentiation of fibroblasts into myofibroblasts.
Jarmuz
Theresa
T
Department of Otolaryngology, Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michael St, Suite 205-M, Atlanta, GA 30322, USA.
Roser
Susanne
S
Rivera
Hilda
H
Gal
Anthony
A
Roman
Jesse
J
D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D005347:Fibroblasts / Q000473:pathology*; D005764:Gastroesophageal Reflux / Q000473:pathology; D005931:Glottis / Q000473:pathology; D007150:Immunohistochemistry; D007829:Laryngostenosis / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1
D000199:Actins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1