Efeito do ácido trans-cinâmico na transdiferenciação epitelial-mesenquimal em células do epitélio alveolar

Abstract

The epithelial-mesenchymal transition (EMT) is a process of transdifferentiation in which epithelial cells start to show a mesenchymal phenotype. It can occurs in a physiological form, as in embryogenesis or in a pathological form, as in fibrotic responses. In chronic inflammation conditions, EMT has an important role on the pathogenesis of fibrosis. Fibrosis is caused by excessive deposition of extracellular matrix components and loss of function of the original tissue. The main effector cell in fibrosis is the myofibroblast, which during a chronic inflammatory response accumulates in the tissue due to the differentiation of fibroblasts and due to the transdifferentiation of epithelial cells. Scientific studies published in the last decade indicate that the inhibition of events associated to EMT reduce the progression of the fibrotic process on tissues, suggesting that EMT is a potential target for treatment of fibrotic disorders. Fibrotic diseases have a great impact on populational health. However, there is yet no cure for fibrosis and the available drugs are not efficient. In the attempt to search for new molecules with therapeutic potential, natural products have been promising for pharmacological research. Phenolic compounds from the cinnamic acid class have showed anti-inflammatory, antioxidant and anti-bacterial effects. The trans-cinnamic acid (TCA) is the most present isoform of cinnamic acid in nature and its potential effects on EMT in the fibrosis context are not reported in the scientific literature until now. In this context, the objective of this project was to investigate the effect of trans-cinnamic acid in vitro on morphological and molecular aspects associated to the epithelial-mesenchymal transdifferentiation on human alveolar epithelial cells. For this were used human cells of the A549 line. The cytotoxic effect of TCA was evaluated by the MTT method. Cells were treated with TGF-β to induce EMT. After 24 h after TCA treatment, morphological aspects were observed through microscopy and fibronectin production (a mesenchymal molecular markers) were quantified by fluorescent microscopy. The migratory capacity was measured by the scratch-wound healing assay. Results of this study showed no cytotoxic effect at low concentrations. TCA inhibited the production of fibronectin and the migratory capacity of cells and seem to affect cell morphology. Taken together, the results of the present study are new in the scientific literature, and suggest that TCA has a potential modulator effect on EMT process.