TY - JOUR
T1 - Modulation of the EMT/MET process by pyrrole-imidazole polyamide targeting human transforming growth factor-β1
AU - Saito, Kosuke
AU - Fukuda, Noboru
AU - Shinohara, Ken Ichi
AU - Masuhiro, Yoshikazu
AU - Hanazawa, Shigemasa
AU - Matsuda, Hiroyuki
AU - Fujiwara, Kyoko
AU - Ueno, Takahiro
AU - Soma, Masayoshi
N1 - Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
PY - 2015/8/19
Y1 - 2015/8/19
N2 - 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.
AB - 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.
KW - Epithelial-mesenchymal transition
KW - Mesenchymal-epithelial transition
KW - Pyrrole-imidazole polyamide
KW - Transforming growth factor-β1
UR - http://www.scopus.com/inward/record.url?scp=84939229933&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2015.07.011
DO - 10.1016/j.biocel.2015.07.011
M3 - Article
C2 - 26222185
AN - SCOPUS:84939229933
SN - 1357-2725
VL - 66
SP - 112
EP - 120
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
ER -