Exp Mol Med.  1999 Jun;31(2):71-75.

Induction of fibronectin gene expression by inhibitors of protein phosphatase type 2B in normal and transformed fibroblasts

• Rhew JH
• Shin YA
• Lee BH
• Park RW
• Kim IS

Abstract

Two intracellular signal pathways mediated by cAMP and protein kinase C (PKC) were involved in the regulation of FN gene expression (Lee et al., Exp. Mol. Med. 30: 240, 1998). In this study, a possible involvement of protein phosphatase-dependent pathways in the regulation of FN gene expression was investigated by using protein phosphatase type 2B (PP2B) inhibitors, cyclosporin A and ascomycin. Both cyclosporin A and ascomycin increased the levels of FN mRNA in WI-38 human lung fibroblasts and the SV40-transformed WI-38 cells but not in MC3T3-E1 osteoblasts. The expression of FN appears to increase from six hours up to 48 hours after treatment suggesting that it is not an immediate effect. In addition, this effect required a new protein synthesis. Neither cyclosporin A nor ascomycin affects the phorbol myristate acetate (PMA)-induced stimulation of FN gene expression and the same result occurred in vice versa suggesting the mechanism of PMA and cyclosporin A/ascomycin in the regulation of FN gene expression may share a common downstream pathway. Taken together, this study suggests that PP2B is involved in the regulation of FN gene expression in normal and transformed fibroblasts but not in osteoblasts.

Keyword

ascomycin; cyclosporin A; fibroblasts; fibronectin; protein phosphatase 2B

MeSH Terms

Animal
Calcineurin/antagonists & inhibitors*
Cell Line, Transformed
Cell Transformation, Viral
Cyclosporine/pharmacology*
Enzyme Inhibitors/pharmacology
Fibroblasts
Fibronectins/metabolism
Fibronectins/genetics*
Gene Expression Regulation*
Human
Lung/cytology
Mice
Osteoblasts
Tacrolimus/pharmacology
Tacrolimus/analogs & derivatives*