title: Epidermal growth factor promotes transforming growth factor-β1-induced epithelial-mesenchymal transition in HK-2 cells through a synergistic effect on Snail.
abstract: Epithelial-mesenchymal transition (EMT) is a central mechanism for wound healing, tissue repair, organ fibrosis and carcinoma progression in adults. Evidence shows that both epidermal growth factor (EGF) and transforming growth factor-β1 (TGF-β1) are upregulated during renal interstitial fibrosis, and that co-stimulation of EGF and TGF-β1 could induce renal tubular epithelial cells to undergo EMT more effectively than EGF or TGF-β1 alone. This study was intended to explore the molecular mechanism underlying this effect. HK-2 cells underwent apparent EMT with increased cell motility after co-stimulation of EGF and TGF-β1 as compared with TGF-β1 or EGF alone. Co-stimulation of EGF and TGF-β1 resulted in rapid and robust ERK1/2 activation and induced persistent high expression of Snail protein. Treatment with the MEK inhibitor U0126 followed by co-stimulation with EGF and TGF-β1 prevented the upregulation of Snail protein, EMT and motility, without impairing Snail mRNA. TGF-β1 induced Snail at the transcriptional level, which was not influenced by EGF. Inhibition of Snail expression by siRNA interference also prevented EMT caused by co-stimulation of EGF and TGF-β1. These data suggest that EGF promotes TGF-β1-induced EMT through a synergistic effect on Snail at the post-transcriptional level in HK-2 cells.
authors.affiliation: Department of Histology and Embryology, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiong
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Kaihong
authors.initials: K
authors.lastname: Ji
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Houqi
authors.initials: H
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D004815:Epidermal Growth Factor / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D000071250:Snail Family Transcription Factors; C508960:TGFB1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases