Abstract
Abstract: :
Purpose:Stress is an organism response to noxious stimulation. We created a mouse model to investigate the gene expression profile of a stress response in the lacrimal gland following a noxious stimulation to the cornea. Methods: Female BALBc mice of 12 weeks of age received a single stimulation with silver nitrate on their both eyes. RNA was extracted from their lacrimal glands over an extended time course. Mouse spotted cDNA microarray was used to monitor the differential gene expression that was analyzed by permutation test in R program with criteria of a 1.5 fold or greater change and a p–value of 0.01. Results: A total of 15,065 genes were evaluated over 8 time points at 0.5, 1, 3, 8, 24, 72, 120 and 360 hours. Out of the 15,065 genes, a total of 13,062 were found to be expressed in the mouse lacrimal gland. Among them, 3811 genes (28.9%) had significantly altered expression, including 1530 known (40.1 %) and 2281 unknown (59.9 %). Many genes had significantly altered expression at multiple time points. Overall, 56.9 % of significant changes in gene expression were down–regulation, and 43.1 % were up–regulation. For the known genes, 80.0 % were down–regulated and only 20.0 % were up–regulated, whereas, for the unknown genes, 38.7 % were down–regulated and 61.3 % were up–regulated. The analysis of known genes showed a broad and long–lasting gene suppression in most functional gene groups including housekeeping, energy metabolism, protein degradation, DNA and protein synthesis, and apoptosis–associated genes. The highest activity of changed expression for known genes occurred at 1 hour and gradually recovered at 120 and 360 hours. Strikingly, heat shock genes were first down–regulated and then up–regulated with a peak activity at 8 hours. Conclusion: This is the first evidence of mass suppression of gene expression from an in vivo stress in which a protection mechanism may be involved.
Keywords: lacrimal gland • stress response • gene microarray