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Hyperosmotic stress induces cell cycle arrest in retinal pigmented epithelial cells

par Arsenijevic, Tatjana ;Vujovic, Anja ;Libert, Frédérick ;Op De Beeck, Anne ;Hebrant, Aline ;Janssens, Sarah;Grégoire, Françoise ;Lefort, Anne ;Bolaky, Nargis ;Perret, Jason ;Caspers, Laure ;Willermain, Francois ;Delporte, Christine
Référence Cell death and disease, 4, page (662)
Publication Publié, 2013

Article révisé par les pairs

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Résumé :

Regulation of water movement is crucial for normal retinal function. Under physiologicalconditions, water is passively transported, following an osmotic gradient, through retinalpigment epithelial (RPE) cells from the subretinal space to the choroid. During macularoedema, occurring in several eye diseases, fluid distribution is profoundly changed and retinalcells potentially exposed to hyperosmotic conditions. We investigated the effect ofhyperosmotic stress on RPE cells using a microarray approach. Upon exposure 4h to 100mMNaCl or 200mM sucrose, 79 were down-regulated and 72 up-regulated. Three gene ontologycategories were significantly modulated: cell proliferation, transcription from RNApolymerase II promoter and response to abiotic stimulus. FACS analysis further demonstratedthat hyperosmotic stimulation for 24h, cell count and cell proliferation were significantlydecreased, as well as the percentage of cells in G0/G1 and S phases, while the percentage ofcells in G2/M phases increased and apoptosis and necrosis remained unaffected. Accordingly,hyperosmotic conditions induced a decrease of cyclin B1 and D1 expression and an activationof the p38 MAP kinase. In conclusion, our results demonstrate that hypertonic conditionsprofoundly affect RPE cell gene transcription regulating cell proliferation by down-regulationcyclin D1 and cyclin B1 protein expression. These findings may contribute to ourunderstanding of macular oedema pathophysiology.