The dual functions of GPI-anchored PH-20: Hyaluronidase and intracellular signaling

Hyaluronan (HA) is synthesized in high-molecular-weight form at the apical pole of airway epithelial cells, covering the luminal surface. When human airway epithelial cells grown and redifferentiated at the air–liquid interface (ALI) were exposed to xanthine/xanthine oxidase (X/XO), ciliary beat frequency (CBF) increased. This effect was blocked by superoxide dismutase (SOD) and catalase. Inhibition of hyaluronan synthesis inhibited the CBF response to X/XO, while addition of exogenous HA amplified it. A functionally blocking antibody to the receptor for hyaluronic acid–mediated motility (RHAMM) reduced the CBF response to X/XO. Since RHAMM has no transmembrane domain and thus cannot signal on its own, the association of RHAMM with recepteur d'origine nantais (RON), a member of the hepatocyte growth factor receptor family, was explored. Immunohistochemistry of human airway epithelium showed co-localization of RHAMM and RON at the apex of ciliated cells. Physical association of RHAMM and RON was confirmed with co-immunoprecipitations. Macrophage-stimulating protein (MSP), an agonist of RON, stimulated CBF. Genistein, a nonspecific tyrosine kinase inhibitor, and MSP β chain (β-MSP), a specific RON inhibitor, blocked the X/XO-induced CBF increase. HA present in the apical secretions of human airway epithelial cells was shown to degrade upon exposure to X/XO, a process inhibited by SOD. Low-molecular-weight HA fragments stimulated CBF, an effect blocked by anti-RHAMM antibody and genistein. These data suggest that high molecular form HA is broken down by reactive oxygen species to form low-molecular-weight fragments that signal via RHAMM and RON to stimulate CBF.

https://www.atsjournals.org/doi/pdf/10.1165/rcmb.2006-0413OC

Apical Oxidative Hyaluronan Degradation Stimulates Airway Ciliary Beating via RHAMM and RON

CHAPTER 2 – Fertilization in Mammals

Effect of hyaluronan supplementation on boar sperm motility and membrane lipid architecture status after cryopreservation.

Hyaluronan (HA) is a non-sulphated glycosaminoglycan polymer naturally occurring in many tissues and fluids of mammals, including the reproductive system Its biosynthesis by HA synthase (HAS1-3) and catabolism by hyaluronidases (HYALs) are affected by ovarian steroid hormones Depending upon its molecular size, HA functions both as a structural component of tissues in the form of high-molecular-weight HA or as a signalling molecule in the form of small HA molecules or HA fragments with effects mediated through interaction with its specific cell-membrane receptors HA is produced by oocytes and embryos and in various segments of the reproductive system This review provides information about the expression and function of members of the HA system, including HAS, HYALs and HA receptors We examine their role in various processes from folliculogenesis through oocyte maturation, fertilisation and early embryo development, to pregnancy and cervical dilation, as well as its application in assisted reproduction technologies Particular emphasis has been placed upon the role of the HA system in pre-implantation embryo development and embryo implantation, for which we propose a hypothetical sequential model

/pdf/regulation-and-roles-of-the-hyaluronan-system-in-mammalian-2ng9io8r4f.pdf

Regulation and roles of the hyaluronan system in mammalian reproduction

The present study was carried out to explore the mechanisms underlying hyaluronan-induced sperm motility. We demonstrate for the first time the enhanced cellular protein phosphorylation in hyaluronic acid stimulated cauda spermatozoa. Labeling of spermatozoa with [Pi] orthophosphoric acid yielded a wide range of labeled phosphoproteins in presence of hyaluronan. Under these experimental conditions, we further show tyrosine specific phosphorylation of proteins. In addition, this is also the first report showing enhanced phosphorylation of 34 kDa hyaluronan binding protein in response to hyaluronan. The role of 34 kDa hyaluronan binding protein in hyaluronan-induced spermatozoa is supported by elevated production of inositol triphosphate accompanied by increased phosphorylation in Triton X-100 insoluble cytoskeletal proteins. The evidence strongly suggests the biological importance of hyaluronan binding protein phosphorylation in the transduction of signals resulting from the interaction of hyaluronate with the sperm surface.

Ranganathan S

Papers

Hyaluronan mediates sperm motility by enhancing phosphorylation of proteins including hyaluronan binding protein.