Induction of fibronectin gene expression by inhibitors of protein phosphatase type 2B in normal and transformed fibroblasts.
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.
Department of Biochemistry, School of Medicine, Kyungpook National University, Taegu, Korea.
J H
JH
Rhew
Y A
YA
Shin
B H
BH
Lee
R W
RW
Park
I S
IS
Kim
D000818:Animals; D065095:Calcineurin Inhibitors; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000166:cytology; D051379:Mice; D010006:Osteoblasts; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D005353:Fibronectins; D016572:Cyclosporine; C058028:immunomycin; D016559:Tacrolimus