Epidermal growth factor induces fibronectin expression in human dermal fibroblasts via protein kinase C delta signaling pathway.
Epidermal growth factor (EGF) and fibronectin are known to play an important role in wound healing. In this study, we demonstrated that EGF upregulates the expression of fibronectin mRNA and protein in human dermal fibroblasts. Actinomycin D, an RNA synthesis inhibitor, significantly blocked basal mRNA expression, but the addition of EGF compensated the blockage. Cycloheximide, a protein synthesis inhibitor, did not block this upregulation by EGF. In addition, the treatment with EGF significantly reduced the degradation rate of fibronectin mRNA. But EGF did not increase fibronectin promoter activity. EGF-mediated induction of fibronectin expression was inhibited by the treatment of fibroblasts with protein kinase C (PKC) inhibitor, Calphostin C and Rottlerin. The transfection of a dominant-negative mutant of PKCdelta into fibroblasts significantly reduced the induction of fibronectin protein expression by EGF. EGF enhanced PKCdelta protein expression and also translocated PKCdelta to the membrane. Rottlerin blocked the EGF-mediated reduction of mRNA degradation rate. These results indicate that EGF-mediated induction of fibronectin expression occurs at the post-transcriptional level and involves PKCdelta signaling pathway.
Mimura
Yoshihiro
Y
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Ihn
Hironobu
H
Jinnin
Masatoshi
M
Asano
Yoshihide
Y
Yamane
Kenichi
K
Tamaki
Kunihiko
K
D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D000098:Acetophenones; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D005353:Fibronectins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; C085746:rottlerin; C496628:PRKCA protein, human; C497258:PRKCD protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon