Lubricin/proteoglycan 4 detected in vocal folds of humans and five other mammals

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.

Potential Pulse-Facilitated Active Adsorption of Lubricin Polymer Brushes Can Both Accelerate Self-Assembly and Control Grafting Density

“…Lubricin (LUB) is one of the human body’s primary boundary lubricant molecules . LUB is a product of the proteoglycan 4 (PRG4) gene and has been identified in vertebrates, ranging from fish to humans, where the gene is highly conserved. − Recently, the LUB extent of function and number of tissues that it can be found has considerably expanded. It is present on the surfaces of joint tissues, in synovial fluids, periodontal ligaments, cornea, tendons, intervertebral discs, and in a variety of other organs.…”

“…It is present on the surfaces of joint tissues, in synovial fluids, periodontal ligaments, cornea, tendons, intervertebral discs, and in a variety of other organs. In terms of function, LUB plays an important role in boundary lubrication, antiadhesion, binding to immune systems cells, and modulation of immune response through toll-like receptors. ,,, Further to all these biological properties, LUB demonstrates the capability of self-assembling in a well-organized “telechelic” polymer brush on a vast array of substrates (i.e., metallic, polymeric, and inorganic surfaces), which makes it an interesting antifouling coating for surfaces and interfaces targeting a variety of applications such as in biosensors, microfluidics, and bionic implants. − …”

“…In terms of function, LUB plays an important role in boundary lubrication, antiadhesion, binding to immune systems cells, and modulation of immune response through toll-like receptors. 3,4,10,11 Further to all these biological properties, LUB demonstrates the capability of selfassembling in a well-organized "telechelic" polymer brush 12 on a vast array of substrates (i.e., metallic, polymeric, and inorganic surfaces), 13 which makes it an interesting antifouling coating 5 for surfaces and interfaces targeting a variety of applications such as in biosensors, microfluidics, and bionic implants. 13−16 Our research group has previously demonstrated the versatility of LUB on different surface materials in terms of preventing nonspecific adsorption of biomolecules (i.e., proteins).…”

Restricted Water Intake Adversely Affects Rat Vocal Fold Biology

“…10,11 Hyaluronan synthase 2 (Has2), hyaluronidase-1 (Hyal1) and hyaluronidase-2 (Hyal2) are enzymes responsible for biosynthesis and degradation of HA, contributing to HA homeostasis in tissue, 12 and were also included in this study. Proteoglycan 4 (PRG4), a lubricant that enables connective tissues to withstand shearing and frictional forces during motion, 13 was also investigated. Interleukin-1 (IL-1) family of cytokines is primarily associated with innate immunity, which can function as a mechanism of host defense.…”