Thymic stromal lymphopoietin induced early stage of epithelial-mesenchymal transition in human bronchial epithelial cells through upregulation of transforming growth factor beta 1

摘要

Purpose: Epithelial-mesenchymal transition (EMT) involved in asthmatic airway remodeling. Thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine, was a key component in airway immunological response in asthma. But the role of TSLP in the EMT process was unknown. We aimed to access whether TSLP could induce EMT in airway epithelia and its potential mechanism. Materials and Methods: Human bronchial epithelial (HBE) cells were incubated with TSLP or transforming growth factor beta 1 (TGF-β1) or both. SB431542 was used to block TGF-β1 signal while TSLP siRNA was used to performed TSLP knockdown. Changes in E-cadherin, vimentin, collagen I and fibronectin level were measured by real-time PCR, western blot and immunofluorescence staining. Expressions of TGF-β after TSLP administration were measured by real-time PCR, western blot and ELISA. Results: TSLP induced changes of EMT relevant markers alone and promoted TGF-β1-induced EMT in HBEs. Intracellular and extracellular expression of TGF-β1 were upregulated by TSLP. SB431542 blocked changes of EMT relevant markers induced by TSLP. Knockdown of TSLP not only reduced TSLP and TGF-β1 expression but also inhibited changes of EMT relevant markers induced by TGF-β1 in HBEs. Conclusions: TSLP could induce early stage of EMT in airway epithelial cells through upregulation of TGF-β1. This effect may act as a targeting point for suppression of asthma.