Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis. Recent studies revealed that pleural mesothelial cells (PMCs) undergo epithelial-mesenchymal transition (EMT) and play a pivotal role in IPF. In animal model, bleomycin induces pulmonary fibrosis exhibiting subpleural fibrosis similar to what is seen in human IPF. It is not known yet whether bleomycin induces EMT in PMCs. In the present study, PMCs were cultured and treated with bleomycin. The protein levels of collagen-I, mesenchymal phenotypic markers (vimentin and α-smooth muscle actin), and epithelial phenotypic markers (cytokeratin-8 and E-cadherin) were measured by Western blot. PMC migration was evaluated using wound-healing assay of culture PMCs in vitro, and in vivo by monitoring the localization of PMC marker, calretinin, in the lung sections of bleomycin-induced lung fibrosis. The results showed that bleomycin induced increases in collagen-I synthesis in PMC. Bleomycin induced significant increases in mesenchymal phenotypic markers and decreases in epithelial phenotypic markers in PMC, and promoted PMC migration in vitro and in vivo. Moreover, TGF-β1-Smad2/3 signaling pathway involved in the EMT of PMC was demonstrated. Taken together, our results indicate that bleomycin induces characteristic changes of EMT in PMC and the latter contributes to subpleural fibrosis.
Phytoestrogens are a family of diverse polyphenolic compounds derived from nature plant that structurally or functionally mimic circulating estrogen in the mammalian reproductive system. They induce estrogenic and anti-estrogenic effects in the brain-pituitary-gonad axis (a principal endocrine system involving in reproductive regulation) and peripheral reproductive organs. The dichotomy of phytoestrogen-mediated actions elucidates that they play the biological activities via complex mechanisms and belong to various chemical classes. In comparison with their unobvious physiological functions in normal reproductive tissues, there are increasing investigations showing that phytoestrogen induces significant inhibitory effects on the growth of breast and ovarian cancers through different signaling pathways. This review summarized the results of the previous studies regarding principal signaling transductions for mediating the growth of the ovarian and breast cancers. Phytoestrogen potentially modulates the signaling molecules via: (1) blocking the nuclear and membrane estrogen receptors (ER), (2) interfering with the growth factor receptor, (3) inhibiting the G protein-coupled receptor in ER-deficient cells, (4) activating apoptosis and nullifying anti-apoptotic signals.
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