Effect of phlorotannins on myofibroblast differentiation and ECM protein expression in transforming growth factor 1-induced nasal polyp-derived fibroblasts

Phlorotannins (PTNs), a group of phenolic compoundsfromseaweeds,havediversebioactivities.However, there has been no report on their antifibrotic effects during nasal polyp (NP) formation. In the present study, the effect of PTNs on transforming growth factor (TGF)- 1-induced profibrotic responses in nasal polyp-derived fibroblasts (NPDFs) were determined and the relevant signaling pathways were investigated. The expression levels of collagen type-1 (col-1) and fibronectin in NP tissues were measured by western blot analysis and immunohistochemistry. The NPdFs were treated with TGF- 1 (1 ng/ml) in the presence or absence of PTNs (5-30 g/ml). The expression levels of a-smooth muscle actin (a-SMA),Col-1,fibronectin,andphosphorylated-smallmothers against decapentaplegic (Smad)2/3 in NPdFs were measured by western blot analysis. The contractile activity of the NPdFs was determined by a collagen gel contraction assay. col-1 and fibronectin proteins were found to be expressed in NP tissues. PTNs had no significant cytotoxic effect on TGF- 1-induced NPdFs. TGF- 1 induced the expression a-SMA, col-1 and fibronectin, and stimulated fibroblast-mediated contraction of collagen gel. However, pre-treatment with PTNs inhibited the expression of these proteins. The inhibitory effects were mediated through the suppression of Smad2/3 signaling pathways in TGF- 1-induced NPdFs. These resulted suggested that PTNs may be important in inhibiting myofibroblast differentiation and extracellular matrix protein accumulation in NP formation through the Smad2/3 signaling pathway.