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.
Highlights
Fibronectin (FN) is a large, extracellular matrix (ECM) glycoprotein that functions as both plasma and ECM protein
We reported that ascomycin and cyclosporin A, inhibitors of serine/threonine protein phosphatase type 2B (PP2B), stimulated FN gene expression in WI-38 human lung fibroblasts and its SV-40 transformed derivative, WI38VA13, but not in MC3T3-E1 osteoblasts
In order to determine the effect of a PP2B inhibitor ascomycin on FN mRNA levels in normal and transformed lung fibroblasts, WI-38 and WI-38VA13, respectively and in MC3T3-E1osteoblasts, cells were exposed to ascomycin ranging from 1 to1,000 ng/ml for 24 h and the steady state levels of FN mRNA were determined by Northern blot hybridization
Summary
Abbreviations: FN, fibronectin; PKC, protein kinase C; PP2B, protein phosphatase type 2B; MEM, minimal essential medium; BSA, bovine serum albumin; FBS, fetal bovine serum; PMA, phorbol myristate acetate; PP1, protein phosphatase type 1; PP2A, protein phosphatase type 2A; TGF-β, transforming growth factor-β
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
