Inhibitory Effect of Delphinidin on Extracellular Matrix Production via the MAPK/NF-κB Pathway in Nasal Polyp-Derived Fibroblasts.
OBJECTIVE
Nasal polyps are associated with chronic inflammation of the mucous membranes in the nose and paranasal sinuses and involved in extracellular matrix (ECM) accumulation. Delphinidin promotes ECM degradation in hepatitis and cardiac fibrosis. The aims of this study were to examine the inhibitory effect of delphinidin on TGF-β1-induced myofibroblast differentiation and ECM accumulation, and to determine the underlying mechanisms in nasal polyp-derived fibroblasts (NPDFs).


METHODS
NPDFs were stimulated with TGF-β1, with or without delphinidin, and the expression levels of α-SMA, fibronectin, and collagen type I were determined by RT-PCR, Western blot analysis, and collagen assay. The expression of α-SMA protein was measured by immunocytochemical staining. Mitogen-activated protein kinase and NF-κB activation induced by TGF-β1 were determined by Western blot analysis. The transcriptional activity of NF-κB was measured by luciferase assay.


RESULTS
The expression levels of α-SMA, fibronectin, and collagen type I increased in TGF-β1-stimulated NPDFs. In TGF-β1-induced NPDFs, delphinidin inhibited the expression of α-SMA, fibronectin, and collagen. Inhibitors of MAPK and NF-κB blocked the expression of α-SMA, fibronectin, and collagen type I. Delphinidin suppressed the activation of MAPK and NF-κB induced by TGF-β1 stimulation.


CONCLUSIONS
These results suggest that delphinidin may inhibit TGF-β1-induced myofibroblast differentiation and ECM production through the MAPK/NF-κB signaling pathway in NPDFs.
Brain Korea 21 Plus for Biomedical Science, Korea University, College of Medicine, Seoul, Korea.; Institute for Medical Devices Clinical Trial Center, Korea University, College of Medicine, Seoul, Korea.
Jung Sun
JS
Cho
Brain Korea 21 Plus for Biomedical Science, Korea University, College of Medicine, Seoul, Korea.
Ju Hyung
JH
Kang
Guro Hospital Department of Otorhinolaryngology Head and Neck Surgery, Korea University, College of Medicine, Seoul, Korea.
Jae Min
JM
Shin
Guro Hospital Department of Otorhinolaryngology Head and Neck Surgery, Korea University, College of Medicine, Seoul, Korea.
Il Ho
IH
Park
Brain Korea 21 Plus for Biomedical Science, Korea University, College of Medicine, Seoul, Korea.; Institute for Medical Devices Clinical Trial Center, Korea University, College of Medicine, Seoul, Korea.; Guro Hospital Department of Otorhinolaryngology Head and Neck Surgery, Korea University, College of Medicine, Seoul, Korea. lhman@korea.ac.kr.
Heung Man
HM
Lee
Chronic rhinosinusitis; MAPK; NF-κB; TGF-β1; delphinidin; extracellular matrix; myofibroblast; nasal polyposis