Avaliação da atividade reguladora do cinamato de metila sobre fibroblastos

Abstract

Fibroblasts are widely recognised for their crucial role in the deposition and remodelling of the extracellular matrix (ECM). However, deregulated activation of fibroblasts results in excessive accumulation of ECM, a phenomenon directly associated with the development of fibrotic diseases such as liver cirrhosis and Chronic obstructive pulmonar disease (COPD). Among the factors involved in the formation of the fibrotic environment, transforming growth factor beta-1 (TGF-β1) plays a central role in the migration and differentiation of fibroblasts under pathological conditions. In this context, the search for compounds capable of modulating fibroblast activation represents a promising strategy for developing effective therapies. Based on the fact that products of natural origin may contain substances with therapeutic potential for fibrogenic conditions, this study aimed to investigate the effect of a hydroxycinnamic acid derivative on fibroblast activation. We selected methyl cinnamate (MC) because of its anti-inflammatory and antioxidant properties. To this end, we used mouse fibroblasts of the L929 strain maintained in DMEM culture medium, subjected to treatment with different concentrations of CM and stimulated with TGF-β1. Our findings show that CM was able to attenuate the activation of fibroblasts stimulated with TGF β1, leading to a reduction in cell migration and the production of extracellular matrix proteins, without compromising cell viability. Mechanically, CM inhibited the nuclear translocation of phosphorylated Smad3 (p-Smad3), a transcription factor critical to the TGF-β1 signalling pathway. Thus, CM showed significant effects in inhibiting phenomena associated with the tissue fibrogenic state, which potentially places it as a promising candidate for the treatment of fibrosis.