KGF and BMP-6 intervene in cellular reprogramming and in mesenchymal-epithelial transition (MET) of 3T3L1 mouse adipose cells

Abstract

Mesenchymal-epithelial transition (MET) is an inevitable process for cellular reprogramming. MET could be induced by suppressing epithelial-mesenchymal transition (EMT) signaling and activating an epithelial program within the cells. Aiming at MET, we investigated the potential of keratinocyte growth factor (KGF) and bone morphogenetic protein (BMP)-6 separately for the induction of MET in 3T3L1 mouse adipose cells and to trace the molecular events that probably upregulate during MET induction. KGF successfully induced MET through upregulation of epithelial related genes and transcript expression on 3T3L1 cells. In contrast, BMP-6 plays completely the reverse role through downregulation of all epithelial related genes and transcript expression. In KGF based treatment, seven genes (K8, K18, EpCAM, K5, K14, SMN1 and α-SMA) out of a total of eight genes were significantly (P<0.05/P<0.01) upregulated. Immunostaining and immunoblotting also revealed significant (P<0.05/P<0.01) expression of several epithelial-specific surface antigens and transcripts. Moreover, Ayoub Shaklar staining (specific to keratin) of KGF treated cells showed formation of keratin (reddish brown color) within cytoplasm of the cells, whereas control and BMP-6 treated cells did not. Conclusively, KGF was observed to have the potential to enhance MET and these clues could be used in future research into cellular reprogramming and regenerative medicine. © 2014 International Federation for Cell Biology.