Simvastatin attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells.
نویسندگان
چکیده
BACKGROUND Transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) may contribute to idiopathic pulmonary fibrosis (IPF). TGF-β1-induced EMT in A549 cells (a human AEC cell line) resulted in the adoption of mesenchymal responses that were predominantly mediated via the TGF-β1-Smad2/3 signaling pathway. Simvastatin (Sim), a 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitor, has been previously reported to inhibit EMT in human proximal tubular epithelial cells and porcine lens epithelial cells and to suppress Smad2/3 phosphorylation in animal models. However, whether Sim can attenuate TGF-β1-induced EMT in A549 cells and its underlying mechanisms remains unknown. METHODS Cells were incubated with TGF-β1 in the presence or absence of Sim. The epithelial marker E-cadherin (E-Cad) and the mesenchymal markers, α-smooth muscle actin (α-SMA), vimentin (Vi) and fibronectin (FN), were detected using western blotting analyses and immunofluorescence. Phosphorylated Smad2 and Smad3 levels and connective tissue growth factor (CTGF) were analyzed using western blotting. In addition, a cell migration assay was performed. Moreover, the levels of matrix metalloproteinase (MMP)-2 and -9 in the culture medium were examined using ELISA. RESULTS Sim significantly attenuated the TGF-β1-induced decrease in E-Cad levels and elevated the levels of α-SMA, Vi and FN via the suppression of Smad2 and Smad3 phosphorylation. Furthermore, Sim inhibited the mesenchymal-like responses in A549 cells, including cell migration, CTGF expression and secretion of MMP-2 and -9. However, Sim failed to reverse the cell morphologial changes induced by TGF-β1 in A549 cells. CONCLUSION Sim attenuated TGF-β1-induced EMT in A549 cells and might be a promising therapeutic agent for treating IPF.
منابع مشابه
Troglitazone Attenuates TGF-β1-Induced EMT in Alveolar Epithelial Cells via a PPARγ-Independent Mechanism
Peroxisome proliferator activated receptor γ (PPARγ) agonists are effective antifibrotic agents in a number of tissues. Effects of these agents on epithelial-mesenchymal transition (EMT) of primary alveolar epithelial cells (AEC) and potential mechanisms underlying effects on EMT have not been well delineated. We examined effects of troglitazone, a synthetic PPARγ agonist, on transforming growt...
متن کاملEpithelial-to-mesenchymal transition of human lung alveolar epithelial cells in a microfluidic gradient device.
Epithelial-to-mesenchymal transition (EMT), a process in which epithelial cells undergo phenotypic transitions to fibrotic cells, is induced by stimulants including transforming growth factor-beta1 (TGF-β1). In the present study, we developed a microfluidic gradient device to reproduce EMT in A549 human lung alveolar epithelial cells in response to TGF-β1 gradients. The device was directly moun...
متن کاملApolipoprotein A1 Inhibits TGF-β1–Induced Epithelial-to-Mesenchymal Transition of Alveolar Epithelial Cells
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported t...
متن کاملGinsenoside Rg1 Attenuates Cigarette Smoke-Induced Pulmonary Epithelial-Mesenchymal Transition via Inhibition of the TGF-β1/Smad Pathway
Epithelial-mesenchymal transition (EMT) is a process associated with airway remodeling in chronic obstructive pulmonary disease (COPD), which leads to progressive pulmonary destruction. Panax ginseng is a traditional herbal medicine that has been shown to improve pulmonary function and exercise capacity in patients with COPD. Ginsenoside Rg1 is one of the main active components and was shown to...
متن کاملNrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
Epithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system, protects cells against oxidative stress. However, it is not known whether Nrf2 regulates snail t...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
دوره 31 6 شماره
صفحات -
تاریخ انتشار 2013