Autophagy regulates TGF-2-induced epithelial-mesenchymal transition in human retinal pigment epithelium cells

Transforming growth factor (TGF)-2-induced epithelial-mesenchymal transition (EMT) in human retinal pigment epithelium (RPE) cells has an important role in the pathophysiology of intraocular fibrotic disorders, which may cause vision impairment and blindness. Autophagy, an intracellular homeostatic pathway, contributes to the physiological and pathological processes of RPE. Furthermore, autophagy has previously been reported to function in the EMT process in numerous tissue and cell types. However, the association between autophagy and the EMT process in RPE cells has not yet been fully determined. The present study demonstrated that TGF-2-treated human RPE cells (ARPE-19 cell line) exhibited a significantly increased autophagic flux compared with control cells, as determined by western blot analysis of the protein levels of microtubule-associated protein 1 light chain 3-II and p62 (also termed sequestosome 1). Furthermore, it was demonstrated that autophagy activation enhanced the TGF-2-induced EMT process in ARPE-19 cells, and inhibition of autophagy by chloroquine administration attenuated TGF-2-induced EMT, which was determined by analyzing the expression of mesenchymal and epithelial markers by reverse transcription-quantitative polymerase chain reaction and/or western blotting. A transwell migration and invasion assays was also performed that demonstrated that autophagy activation by rapamycin enhanced TGF-2-stimulated RPE cell migration and invasion, and inhibition of autophagy reduced TGF-2-stimulated RPE cell migration and invasion. These results also demonstrated that autophagy activation enhanced the TGF-2-induced EMT process in ARPE-19 cells, and inhibition of autophagy attenuated TGF-2-induced EMT. Overall, the results of the present study demonstrated that TGF-2-induced EMT may be regulated by autophagy, thus indicating that autophagy may serve as a potential therapeutic target for the attenuation of EMT in intraocular fibrotic disorders.