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.
Rhew
J H
JH
Department of Biochemistry, School of Medicine, Kyungpook National University, Taegu, Korea.
Shin
Y A
YA
Lee
B H
BH
Park
R W
RW
Kim
I S
IS
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