Changes in expression of extracellular matrix genes, fibrogenic factors, and actin cytoskeletal organization in retinol treated and untreated vocal fold stellate cells

The regulation of extracellular matrix (ECM) constituency is critical in maintaining vocal cord biomechanical viscoelasticity required for phonation. Recently our laboratory successfully isolated and cultured a novel cell called a vocal fold stellate cell (VFSC), thought to play a central role in laryngeal ECM metabolism, aging, scarring and cancer. Our laboratory has shown that these cells undergo transdifferentiation that is partially reversed by exposure to all-trans retinol (ATROH). Here we make the first report on the expression of various ECM components, MMPs, TIMPs, pro-fibrogenic cytokines, and other ECM modulators in transdifferentiated and deactivated VFSCs. We show that VFSCs maintain an ECM expression pattern similar to laryngeal cancer and scars but distinct from tracheal fibroblasts. Exposure to ATROH differentially affects the VFSC expression of ECM components, matrix-regulating enzymes, and fibrogenic factors suggesting that the inhibitory effects of this synthetic cofactor should be studied further in laryngeal fibrosis and scarring. We also show that increased exposure to retinol induces sequential reorganization of the actin cytoskeleton in activated VFSCs. Our findings demonstrate that VFSCs are capable of regulating vocal fold ECM constituency important throughout normal laryngeal development. Furthermore, our results implicate VFSC activation in ECM misregulation which is a hallmark of several laryngeal pathologies.