The effect of sesamin on airway fibrosis in vitro and in vivo.

Abstract

Airway fibrosis, which is a crucial pathological condition occurring in various types of pulmonary disorders, is characterized by accumulation and activation of fibroblast cells, deposition of extracellular matrix (ECM) proteins, and increase of airway basement membrane. Transforming growth factor beta 1 (TGF-β1) is the principal profibrogenic cytokine that is responsible for fibrotic responses. In the present study, we aimed to investigate the antifibrotic effects of the natural polyphenolic compound, sesamin, on TGF-β1-induced fibroblast proliferation and activation, epithelial-mesenchymal transition (EMT), and ovalbumin (OVA)-induced airway fibrosis in vivo. We found that sesamin attenuated TGF-β1-induced proliferation of cultured lung fibroblasts. Sesamin inhibited TGF-β1-stimulated expression of alpha smooth muscle actin (α-SMA), suggesting that sesamin plays an inhibitory role in fibroblast activation. Sesamin blocked upregulation of the mesenchymal markers (fibronectin and vimentin) and downregulation of the epithelial marker (E-cadherin), indicating an inhibitory effect on TGF-β1-induced EMT in A549 cells. TGF-β1-induced Smad3 phosphorylation was also significantly reduced by sesamin in both cultured fibroblast and A549 cells. In the airway fibrosis induced by OVA in mice, sesamin inhibited the accumulation of α-SMA-positive cells and expression of collagen I in the airway. Histological studies revealed that sesamin protected against subepithelial fibrosis by reducing myofibroblast activation and collagen accumulation in the ECM. OVA-induced thickening of basement membrane was significantly alleviated in animals receiving sesamin treatments. These results suggest a therapeutic potential of sesamin as an antifibrotic agent.

• Authors: Ching-Huei Lin, Mei-Lin Shen, Shung-Te Kao, Dong Chuan Wu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 22 Issue 1 Pg. 141-50 (Sep 2014) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 24978608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Actins
• Collagen Type I
• Dioxoles
• Extracellular Matrix Proteins
• Lignans
• Smad3 Protein
• Transforming Growth Factor beta1
• alpha-smooth muscle actin, mouse
• sesamin

Topics

• Actins (genetics, metabolism)
• Animals
• Basement Membrane (drug effects, pathology)
• Cell Line
• Cell Proliferation (drug effects)
• Collagen Type I (metabolism)
• Dioxoles (therapeutic use)
• Down-Regulation
• Epithelial-Mesenchymal Transition (drug effects)
• Extracellular Matrix Proteins (metabolism)
• Fibroblasts (drug effects, physiology)
• Fibrosis
• Humans
• Lignans (therapeutic use)
• Lung Diseases (drug therapy, immunology, pathology)
• Mice
• Mice, Inbred C57BL
• Respiratory Mucosa (drug effects, pathology)
• Signal Transduction (drug effects)
• Smad3 Protein (metabolism)
• Transforming Growth Factor beta1 (immunology)