TGFb reduces airway epithelial proliferation in vitro but stimulates mucosal remodeling deposition) in vivo in its role as a profibrogenic factor. TGFb has three isoforms, TGFb1, TGFb2 and TGFb3. Welham and colleagues reported that TGFb1 and TGFb3 are expressed in injured and uninjured vocal fold mucosa, in cell-specific and time-dependent manners. With regard to epithelium, TGFb1 is expressed in nai¨ve rat stratified squamous epithelial cells and ciliated pseudocolumnar epithelial cells while TGFb3 is expressed in primarily in ciliated pseudocolumnar epithelial cells. Following injury, TGFb1 is observed throughout rat vocal fold mucosa, while TGFb3 is observed primarily in epithelial cells. TGFb1 mRNA expression levels have been quantified in rat vocal fold at various time points during the acute and chronic phases of wound injury; an increase in expression levels was reported at one hour, 3 days, to seven days post-injury. TGFb1 regulates the lamina propria composition through synthesis of ECM component such as collagen, cell proliferation, and cell death. Expression levels in vocal fold lamina propria post-injury have been correlated with histologic changes in the lamina propria during repair; peak TGFb1 levels correlated with deposition of collagen type I and type III, as well as fibronectin. Exogenous TGFb1, the most abundant isoform of the TGFb superfamily, induces collagen Temozolomide 85622-93-1 secretion and myofibroblast differentiation by vocal fold fibroblasts in vitro, indicating a role for the growth factor in scar formation. In vivo experiments have shown that exogenous TGFb1 and TGFb3 reduce vocal fold scar formation post-injury. While, based on literature in other tissue, autocrine and paracrine TGFb1 signaling in vocal fold epithelium is likely, TGFb secretion by epithelial cells has yet to be confirmed. Both EGF and TGFb mediate their effects through activation of the epidermal growth factor receptor, a member of the ErbB family of receptor tyrosine kinases; EGF activates EGFR by binding directly to the receptor while TGFb1 activates or inhibits EGFR indirectly via a signaling pathway. This activation is critical for wound repair, specifically epithelial proliferation and migration. Given the purported effects of EGF and TGFb1 on epithelium outlined above, examination of the distribution of activated EGFR following injury can yield important insights into mucosal remodeling. Increased EGFR expression has been reported in airway epithelium in chronic disease in vivo and following acute injury. Further, EGFR, which are found only on the basolateral membrane of healthy airway epithelial cells and, therefore, are protected from environmental stimuli, are expressed on the apical membrane of these cells following injury thus exposing them to activation by environmental stimuli. This increased expression and altered distribution of EGFR are associated with hyperresponsiveness to environmental stimuli, inflammation, and mucosal remodeling. Similar changes in expression level and distribution of activated EGFR in vocal fold epithelium following injury would support a role for EGFR in mediating vocal fold mucosal remodeling.