The mesenchymal to epithelial transition (MET) occurs in organ development and anti-tumorigenesis. We have investigated the effects of calcium (Ca(2+)) and epidermal growth factor (EGF) on human mesenchymal stem cell (hMSCs) differentiation into epithelial-like cells. hMSCs lost their biological characteristics after EGF transfection, and MET was achieved by adding 0.4 mmol Ca(2+). Western blotting and immunofluorescence showed expression of EGF, keratin, keratin 19 (K19), β1-integrin, E-cadherin and phosphorylated focal adhesion kinase (p-FAK, Ser-910) increased in hMSCs infected with EGF and exposed to Ca(2+), although Smad3 activation was downregulated. hMSCs co-stimulated with EGF transfection and Ca(2+) can therefore differentiate into epithelial-like cells in vitro.

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