Induction of fibronectin gene expression by inhibitors of protein phosphatase type 2B in normal and transformed fibroblasts.
- Author:
Jung Hwa RHEW
1
;
Young Ah SHIN
;
Byung Heon LEE
;
Rang Woon PARK
;
In San KIM
Author Information
1. Department of Biochemistry, School of Medicine, Kyungpook National University, Taegu, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
ascomycin;
cyclosporin A;
fibroblasts;
fibronectin;
protein phosphatase 2B
- MeSH:
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*
- From:Experimental & Molecular Medicine
1999;31(2):71-75
- CountryRepublic of Korea
- Language:English
-
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.
