title: Modulation of the EMT/MET process by pyrrole-imidazole polyamide targeting human transforming growth factor-β1.
abstract: Transforming growth factor-β1 (TGF-β1) is a potent induction factor for epithelial-mesenchymal transition (EMT). Mesenchymal-epithelial transition (MET), as the inverse process of EMT, has recently been reported to promote the induction of induced pluripotent stem cells (iPSCs). We have developed pyrrole-imidazole (PI) polyamide, a novel gene regulator that targets human TGF-β1, and investigated its effects on the EMT/MET process. PI polyamide targeted to TGF-β1 significantly inhibited the mRNA expression of TGF-β1 and SNAI1 as an EMT marker and increased mRNA and protein expression of E-cadherin in human epithelial cells. To enhance the induction of iPSCs by the MET process, PI polyamide targeted to TGF-β1 was applied to human fibroblasts transfected with exogenous reprogramming factors by Sendai virus vector and grown in human iPSCs. The PI polyamide significantly increased the number of alkaline phosphatase-positive colonies. The expression of undifferentiated markers was also observed in these colonies. These results suggest that PI polyamide targeted to human TGF-β is a novel compound that can control the EMT/MET process of human epithelial cells and enhance the induction of human fibroblasts to iPSCs.
authors.affiliation: Department of General Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Saito
authors.affiliation: Division of Life Science, Advanced Research Institute for the Sciences and Humanities, Nihon University Graduate School, Tokyo, Japan; Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: fukuda.noboru@nihon-u.ac.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.affiliation: Division of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Shinohara
authors.affiliation: Department of Applied Biological Sciences, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Masuhiro
authors.affiliation: Department of Applied Biological Sciences, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Hanazawa
authors.affiliation: Department of General Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: Department of General Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of General Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism; D018613:Microscopy, Confocal; D009757:Nylons / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C029899:imidazole; D013755:Tetradecanoylphorbol Acetate
keywords: Epithelial–mesenchymal transition; Mesenchymal–epithelial transition; Pyrrole–imidazole polyamide; Transforming growth factor-β1