title: Differential effect of rebamipide on transmembrane mucin biosynthesis in stratified ocular surface epithelial cells.
abstract: Mucins are a group of highly glycosylated glycoproteins responsible for the protection of wet-surfaced epithelia. Recent data indicate that transmembrane mucins differ in their contribution to the protective function of the ocular surface, with MUC16 being the most effective barrier on the apical surface glycocalyx. Here, we investigated the role of the mucoprotective drug rebamipide in the regulation of transmembrane mucin biosynthesis using stratified cultures of human corneal and conjunctival epithelial cells. We find that the addition of rebamipide to corneal, but not conjunctival, epithelial cells increased MUC16 protein biosynthesis. Rebamipide did not affect the levels of MUC1, 4 and 20 compared to control. In these experiments, rebamipide had no effect on the expression levels of Notch intracellular domains, suggesting that the rebamipide-induced increase in MUC16 biosynthesis in differentiated corneal cultures is not regulated by Notch signaling. Overall these findings indicate that rebamipide induces the differential upregulation of MUC16 in stratified cultures of human corneal epithelial cells, which may have implications to the proper restoration of barrier function in ocular surface disease.
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Uchino
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Woodward
authors.affiliation: Schepens Eye Research Institute and Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. Electronic address: pablo_argueso@meei.harvard.edu.
authors.forename: Pablo
authors.initials: P
authors.lastname: Argüeso
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D018394:CA-125 Antigen / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D015363:Quinolones; D012333:RNA, Messenger; C052785:rebamipide; D000409:Alanine
keywords: Notch signaling; Ocular surface; Rebamipide; Stratified epithelium; Transmembrane mucins