Objectives/hypothesis: Lubricin/proteoglycan-4 (PRG4) lubricates connective tissues such as joints and tendon sheaths, enabling them to better withstand shearing and frictional forces during motion. We wondered whether PRG4 might play a role in phonation, as normal vocal folds withstand repetitive, high-velocity deformations remarkably well. As a first step, we tested whether PRG4 is expressed in vocal folds.
Study design: Laboratory study.
Methods: Anatomical and molecular methods were applied to 47 larynges from humans, macaque (Macaca fascicularis), canines, pigs, calves, and rats. Immunohistochemistry (IHC), Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) methods were used to test for the presence of PRG4.
Results: In all species, the true vocal fold lamina propria (TVF-LP) was positive for PRG4 by IHC, whereas immunoreactivity of the false vocal fold was weak or absent, depending on the species. Human TVF-LP was strongly stained across all layers. Immunoreactivity was seen variably on the vocal fold surface and within the vocal fold epithelium, in the conus elasticus and thyroglottic ligament, and at the tip of vocal process. Western blots of four humans and six pigs demonstrated immunoreactivity at appropriate molecular weight. qRT-PCR of pig tissues confirmed PRG4 mRNA expression, which was highest in the TVF-LP.
Conclusions: PRG4 was found in phonatory tissues of six mammals. We suggest it might act as a lubricant within the lamina propria and possibly on the vocal fold surface, limiting phonation-related damage to vocal fold extracellular matrix and epithelium, and enhancing vocal efficiency by reducing internal friction (viscosity) within the vocal fold.
Level of evidence: NA Laryngoscope, 129:E229-E237, 2019.
Keywords: PRG4; Vocal fold; larynx; lubricin; voice.
© 2019 The American Laryngological, Rhinological and Otological Society, Inc.