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Simvastatin attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells.
Cell Physiol Biochem. 2013; 31(6):863-74.CP

Abstract

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.

Authors+Show Affiliations

Fifth School of Clinical Medicine, Peking University, Beijing, China.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23817018

Citation

Yang, Tuo, et al. "Simvastatin Attenuates TGF-β1-induced Epithelial-mesenchymal Transition in Human Alveolar Epithelial Cells." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 31, no. 6, 2013, pp. 863-74.
Yang T, Chen M, Sun T. Simvastatin attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells. Cell Physiol Biochem. 2013;31(6):863-74.
Yang, T., Chen, M., & Sun, T. (2013). Simvastatin attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 31(6), 863-74. https://doi.org/10.1159/000350104
Yang T, Chen M, Sun T. Simvastatin Attenuates TGF-β1-induced Epithelial-mesenchymal Transition in Human Alveolar Epithelial Cells. Cell Physiol Biochem. 2013;31(6):863-74. PubMed PMID: 23817018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simvastatin attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells. AU - Yang,Tuo, AU - Chen,Miaomiao, AU - Sun,Tieying, Y1 - 2013/06/11/ PY - 2013/05/20/accepted PY - 2013/7/3/entrez PY - 2013/7/3/pubmed PY - 2014/2/19/medline SP - 863 EP - 74 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell Physiol Biochem VL - 31 IS - 6 N2 - 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. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/23817018/Simvastatin_attenuates_TGF_β1_induced_epithelial_mesenchymal_transition_in_human_alveolar_epithelial_cells_ L2 - https://www.karger.com?DOI=10.1159/000350104 DB - PRIME DP - Unbound Medicine ER -