Apigenin alleviates TGF-β1-induced nasal mucosa remodeling by inhibiting MAPK / NF-kB signaling pathways in chronic rhinosinusitis

Background Chronic rhinosinusitis is involved in tissue remodeling of nasal mucosa such as nasal myofibroblast differentiation and extracellular matrix production. Apigenin (4’,5,7-trihydroxyfla-vone) is a bioflavonoid compound and has anti-tissue remodeling characteristics. The aims of this study were to evaluate the effect of apigenin on TGF-β1-induced myofibroblast differentiation and extracellular matrix accumulation and to determine the underlying mechanism. Methods Nasal fibroblasts and ex vivo nasal inferior turbinate tissues were stimulated with TGF-β1 with or without apigenin. The expression levels of α-SMA, fibronectin and collagen type I were determined by real-time PCR, western blot and immunocytochemical staining. Mito-gen-activated protein kinase (MAPK) phosphorylation induced by TGF-β1 were determined by western blot analysis. The transcriptional activity of NF-κB was measured by luciferase assay. Migration effects of fibroblasts were evaluated by wound scratch and transwell migration assay. Contractile activity was determined by collagen gel contraction assay. Results The expression levels of α-SMA, fibronectin, and collagen type I significantly increased in TGF-β1-stimulated nasal fibroblasts. In TGF-β1-stimulated nasal fibroblasts, apigenin inhibited the expressions of α-SMA, fibronectin, and collagen type I. Inhibitors of MAPK (p-38, JNK) and NF-κB blocked the expression of α-SMA, fibronectin and collagen type I. Apigenin suppressed the activation of MAPK (p-38, JNK) and NF-κB induced by TGF-β1 treatment. Apigenin also inhibited the functional activity of fibroblasts by reducing the migration and collagen contractile activities. Conclusions These results suggests the possible use of apigenin as a chronic rhinosinusitis therapeutic agent which can suppress tissue remodeling in nasal mucosa.