Jarmuz Theresa, Roser Susanne, Rivera Hilda, Gal Anthony, Roman Jesse
Department of Otolaryngology, Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michael St, Suite 205-M, Atlanta, GA 30322, USA.
Ann Otol Rhinol Laryngol. 2004 Jun;113(6):488-97. doi: 10.1177/000348940411300614.
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.
声门下狭窄（SGS）的特征是由于结缔组织过度沉积导致气管腔闭塞。我们推测气管损伤会触发转化生长因子-β1（TGF-β1）的早期产生，TGF-β1是一种与纤维增生性疾病有关的因子。反过来，TGF-β1刺激气管成纤维细胞转化为肌成纤维细胞，增加基质产生和瘢痕收缩，这可能对SGS的发展奠定基础有影响。与这一假设一致，对患有SGS的人类和实验性气管损伤大鼠的气管进行组织学分析发现，与对照气管相比，α-平滑肌肌动蛋白阳性细胞增加，表明肌成纤维细胞分化增加。体外暴露于TGF-β1或胃液的大鼠气管成纤维细胞显示α-平滑肌肌动蛋白表达增加、基质分子表达改变以及胶原凝胶收缩增加。这些发现表明，胃液或其他气管损伤因素通过刺激成纤维细胞向肌成纤维细胞分化来促进组织重塑。
