Lubricin/proteoglycan 4 detected in vocal folds of humans and five other mammals
James B. Kobler PhD  Monica A. Tynan BS  Steven M. Zeitels MD  Andrew S. Liss PhD  Maria T. Gianatasio BS  Alyssa A. Morin MSc  Tannin A. Schmidt PhD
First published: 06 January 2019 https://doi.org/10.1002/lary.27783
Editor's Note: This Manuscript was accepted for publication on December 10, 2018.
Presented at the American Bronchoesophageal Association Annual Meeting at the Combined Otolaryngology Spring Meetings, National Harbor, Maryland, U.S.A., April 18–22, 2018.
This work was supported by the Voice Health Institute (j.b.k., m.a.t., s.m.z.), as well as the Canada Research Chairs Program and the University of Connecticut Department of Biomedical Engineering (t.a.s., a.a.m.).
t.a.s. holds patents on recombinant human PRG4, and is a paid consultant for and holds equity in Lubris LLC, Weston, Massachusetts, U.S.A.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
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Abstract
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