Modulation of the EMT/MET process by pyrrole–imidazole polyamide targeting human transforming growth factor-β1. (September 2015)

• Record Type: Journal Article
• Authors: Saito, Kosuke; Fukuda, Noboru; Shinohara, Ken-ichi; Masuhiro, Yoshikazu; Hanazawa, Shigemasa; Matsuda, Hiroyuki; Fujiwara, Kyoko; Ueno, Takahiro; Soma, Masayoshi
• Is Part Of: International journal of biochemistry & cell biology. Volume 66(2015:Sep.)
• Page Start: 112
• Page End: 120
• Publication Date: 2015-09
• Subjects: Epithelial–mesenchymal transition -- Mesenchymal–epithelial transition -- Pyrrole–imidazole polyamide -- Transforming growth factor-β1; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2015.07.011
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: PI polyamide targeting human TGF-β1 gene promoter region regulates the EMT/MET process in MCF10A cells. PI polyamide significantly increased reprogramming efficiency via enhanced MET in iPSC induction of human fibroblasts. PI polyamide to human TGF-β is a novel compound that can control EMT/MET of human epithelial cells. 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.