Lacritin

rdf:langString Lacritin

rdf:langString Lacritin is a 12.3 kDa glycoprotein encoded in humans by the LACRT gene. Lacritin's discovery emerged from a screen for factors that stimulate tear protein secretion. Lacritin is a secreted protein found in tears and saliva. Lacritin also promotes tear secretion, the proliferation and survival of epithelial cells, and corneal wound healing Lacritin is thus a multifunctional prosecretory mitogen with cell survival activity. Natural or bacterial cleavage of lacritin releases a C-terminal fragment that is bactericidal. Most lacritin is produced by the lacrimal gland, including the accessory lacrimal gland of Wolfring. Some lacritin is produced by the meibomian gland, and by epithelial cells of the conjunctiva and cornea. Together these epithelia comprise much of the lacrimal functional unit (LFU). Dry eye is the most common disease of the LFU. A growing number of studies suggest that lacritin may be differentially downregulated in dry eye, including contact lens-related dry eye. Topical lacritin promotes tearing in rabbit preclinical studies. In the Aire knockout mouse model of dry eye (considered similar to human Sjogren's syndrome), topical lacritin restores pilocarpine-induced tearing, largely eliminates lissamine green staining and reduces the size of inflammatory foci in the lacrimal gland. Lacritin cell targeting is dependent on the cell surface heparan sulfate proteoglycan syndecan-1 (SDC1). Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein. A G-protein-coupled receptor (GPCR) then appears to be ligated. Targeted cells signal to NFAT and mTOR if conditions are suitable for proliferation, or to AKT and FOXO3 under conditions of stress.