Purchase this article with an account.
J. Wang, I.M. Hussaini, G.W. Laurie; Lacrimal/Salivary Prosecretory Mitogen ‘Lacritin’ as a Glandular Stem Cell Survival Factor . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3885.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Lacritin is a prosecretory mitogen secreted by human lacrimal acinar and salivary ductal cells which respectively flows via ducts onto the corneal surface or into saliva. Curiously, salivary gland lacritin expression is restricted to a minor fraction of ductal cells that are thought to serve as the stem cell compartment for the entire secretory parenchyma. Here we ask whether lacritin acts as a glandular stem cell survival factor and morphogen, and extend our observations on lacritin–dependent cell signaling. Methods: Lacritin effects were studied in a human stem cell–derived ductal line. Cells from subconfluent serum–free cultures, either untreated or lacritin treated, were examined at various times by FACS, and at culture wound edges for acinar–like ‘morphogenesis’. Untreated or treated cell homogenates were incubated with antibody arrays using anti–phosphotyrosine antibodies for detection, followed by western blotting for individual signaling molecules. Results: FACS analysis revealed that 28 hr or more of lacritin treatment restricted apoptosis to approximately 2 – 5% of cells, versus 18 – 50% of cells in control cultures. Treated cells appear to form lumen–containing structures that were absent in negative and EGF positive controls. Within one minute of adding 10 ng/ml of recombinant human lacritin, a tyrosine phosphorylation, and pertussis toxin–inhibitable calcium cascade is initiated. The pathways involve PKC and possibly calmodulin and NFAT but little or no ERK1/2, JNK, or c–Raf. Neither Cdc42, Rho nor Rac1 appears to be activated. Conclusions: Taken together, these data point to lacritin as a multi–functional factor that may have a larger role in acinar morphogenesis and in the survival of glandular and downstream (possibly corneal) cell populations in a substantially MAPK–, ERK– and JNK–independent manner. Supported by EY013143 (GWL).
This PDF is available to Subscribers Only