BACKGROUND: Chronic persistent asthma is characterized by airway remodeling, in which epithelial-mesenchymal transition (EMT) may play a significant role. Dehydroepiandrosterone (DHEA), a steroid hormone and testosterone analog, is considered as an important immunomodulating hormone. However, its role in EMT remains unclear. We sought to investigate whether transforming growth factor-β1 (TGF-β1) stimulates human bronchial epithelial cells (16HBE-14o) to undergo EMT, and whether this transition can be abrogated by DHEA. METHODS: The 16HBE-14o cells were stimulated with 5 ng/ml TGF-β1 for 3 days to induce EMT, with or without DHEA pretreatment, and assayed for epithelial or mesenchymal markers using Western Blot. The involvement of phosphoinositide 3-kinase (PI3K) -mediated signaling pathway was also evaluated, the epithelial cells were also incubated with pharmacological approaches (agonists and antagonists of Akt, LY294002 or IGF-1) or flutamide, the antagonist of androgen receptor. Results were analyzed using nonparametric statistical tests. RESULTS: Our data demonstrate that treatment of 16HBE-14o cells with TGF-β1 for 3 days induced EMT as reflected by conversion to the spindle-like morphology, loss of E-cadherin, and acquisition of a-smooth muscle actin (a-SMA). Pretreatment of 16HBE-14o cells with DHEA preserved the epithelial-like morphology, restored the expression of E-cadherin, and abolished the activation of a-SMA, and this effect is a PI3K-dependent mechanism. CONCLUSION: Our results indicate that TGF-β1 induces EMT in a PI3K-dependent manner in 16HBE-14o cells. DHEA inhibits the bronchial epithelial to mesenchymal transition via the inhibition of PI3K/Akt-dependent signal pathway stimulated by TGF-β1. Therefore, DHEA may be a useful therapy for asthma.
BACKGROUND: Chronic persistent asthma is characterized by airway remodeling, in which epithelial-mesenchymal transition (EMT) may play a significant role. Dehydroepiandrosterone (DHEA), a steroid hormone and testosterone analog, is considered as an important immunomodulating hormone. However, its role in EMT remains unclear. We sought to investigate whether transforming growth factor-β1 (TGF-β1) stimulates human bronchial epithelial cells (16HBE-14o) to undergo EMT, and whether this transition can be abrogated by DHEA. METHODS: The 16HBE-14o cells were stimulated with 5 ng/ml TGF-β1 for 3 days to induce EMT, with or without DHEA pretreatment, and assayed for epithelial or mesenchymal markers using Western Blot. The involvement of phosphoinositide 3-kinase (PI3K) -mediated signaling pathway was also evaluated, the epithelial cells were also incubated with pharmacological approaches (agonists and antagonists of Akt, LY294002 or IGF-1) or flutamide, the antagonist of androgen receptor. Results were analyzed using nonparametric statistical tests. RESULTS: Our data demonstrate that treatment of 16HBE-14o cells with TGF-β1 for 3 days induced EMT as reflected by conversion to the spindle-like morphology, loss of E-cadherin, and acquisition of a-smooth muscle actin (a-SMA). Pretreatment of 16HBE-14o cells with DHEA preserved the epithelial-like morphology, restored the expression of E-cadherin, and abolished the activation of a-SMA, and this effect is a PI3K-dependent mechanism. CONCLUSION: Our results indicate that TGF-β1 induces EMT in a PI3K-dependent manner in 16HBE-14o cells. DHEA inhibits the bronchial epithelial to mesenchymal transition via the inhibition of PI3K/Akt-dependent signal pathway stimulated by TGF-β1. Therefore, DHEA may be a useful therapy for asthma.
Authors: Joe G Zein; Jeffrey M McManus; Nima Sharifi; Serpil C Erzurum; Nadzeya Marozkina; Timothy Lahm; Olivia Giddings; Michael D Davis; Mark D DeBoer; Suzy A Comhair; Peter Bazeley; Hyun Jo Kim; William Busse; William Calhoun; Mario Castro; Kian Fan Chung; John V Fahy; Elliot Israel; Nizar N Jarjour; Bruce D Levy; David T Mauger; Wendy C Moore; Victor E Ortega; Michael Peters; Eugene R Bleecker; Deborah A Meyers; Yi Zhao; Sally E Wenzel; Benjamin Gaston Journal: Am J Respir Crit Care Med Date: 2021-08-01 Impact factor: 30.528
Authors: Mandy Laube; Elena Amann; Ulrike Uhlig; Yang Yang; Hans W Fuchs; Michael Zemlin; Jean-Christophe Mercier; Rolf F Maier; Helmut D Hummler; Stefan Uhlig; Ulrich H Thome Journal: PLoS One Date: 2017-01-03 Impact factor: 3.240
Authors: Joe Zein; Benjamin Gaston; Peter Bazeley; Mark D DeBoer; Robert P Igo; Eugene R Bleecker; Deborah Meyers; Suzy Comhair; Nadzeya V Marozkina; Calvin Cotton; Mona Patel; Mohammad Alyamani; Weiling Xu; William W Busse; William J Calhoun; Victor Ortega; Gregory A Hawkins; Mario Castro; Kian Fan Chung; John V Fahy; Anne M Fitzpatrick; Elliot Israel; Nizar N Jarjour; Bruce Levy; David T Mauger; Wendy C Moore; Patricia Noel; Stephen P Peters; W Gerald Teague; Sally E Wenzel; Serpil C Erzurum; Nima Sharifi Journal: Proc Natl Acad Sci U S A Date: 2020-01-13 Impact factor: 11.205
Authors: Mark D DeBoer; Brenda R Phillips; David T Mauger; Joe Zein; Serpil C Erzurum; Anne M Fitzpatrick; Benjamin M Gaston; Ross Myers; Kristie R Ross; James Chmiel; Min Jie Lee; John V Fahy; Michael Peters; Ngoc P Ly; Sally E Wenzel; Merritt L Fajt; Fernando Holguin; Wendy C Moore; Stephen P Peters; Deborah Meyers; Eugene R Bleecker; Mario Castro; Andrea M Coverstone; Leonard B Bacharier; Nizar N Jarjour; Ronald L Sorkness; Sima Ramratnam; Anne-Marie Irani; Elliot Israel; Bruce Levy; Wanda Phipatanakul; Jonathan M Gaffin; W Gerald Teague Journal: BMC Pulm Med Date: 2018-04-10 Impact factor: 3.317