NRF2 Activation Inhibits Both TGF‐<i>β</i>1‐ and IL‐13‐Mediated Periostin Expression in Fibroblasts: Benefit of Cinnamaldehyde for Antifibrotic Treatment

Abstract

Systemic fibrosing or sclerotic disorders are life‐threatening, but only very limited treatment modalities are available for them. In recent years, periostin (POSTN), a major extracellular matrix component, was established by several studies as a novel key player in the progression of systemic fibrotic disease. In this research, we revealed the involvement of oxidative stress in the expression of POSTN induced by TGF‐ β 1 and IL‐13 in dermal fibroblasts. We found that the antioxidant cinnamaldehyde activated the NRF2/HMOX1 pathway. Cinnamaldehyde also alleviated TGF‐ β 1‐ and IL‐13‐mediated production of reactive oxygen species and subsequent POSTN upregulation in dermal fibroblasts. In contrast, NRF2 silencing abolished the cinnamaldehyde‐mediated downregulation of POSTN. These results suggest that cinnamaldehyde is a broad inhibitor of POSTN expression covering both TGF‐ β 1 and IL‐13 signaling. Cinnamaldehyde may thus be beneficial for the treatment of systemic fibrotic diseases.