Effect of phlorotannins on myofibroblast differentiation and ECM protein expression in transforming growth factor β1-induced nasal polyp-derived fibroblasts

초록

Phlorotannins (PTNs), a group of phenolic compounds from seaweeds, have diverse bioactivities. 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)-beta 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-beta 1 (1 ng/ml) in the presence or absence of PTNs (5-30 mu g/ml). The expression levels of alpha-smooth muscle actin (alpha-SMA), Col -1,fibronectin, and phosphorylated-small mothers 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-beta 1-induced NPDFs. TGF-beta 1 induced the expression alpha-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-beta 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.

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