Persistent versus transient map kinase (ERK) activation in the proliferation of lung epithelial type 2 cells.
Type 2 pneumocytes are progenitor cells of alveolor epithelium and important for reepithelialization following lung injury. This study examined the role of persistent versus transient mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinase; ERK) in type 2 cell proliferation. Three different types of agents; epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate (TPA), and fetal bovine serum (FBS) induced different patterns of ERK activation. FBS induced a strong and persistent MAP kinase response, whereas the effect of EGF was transient with a strong activation at 5 minutes and only a slight stimulation at 4 hours. The TPA response was more prolonged than the EGF response, but not by far as strong and persistent as the FBS response. Activation by EGF and TPA and the early response induced by FBS were strongly reduced by the MEK inhibitor PD98059. The sustained FBS-induced ERK activation was inhibited by approximately 50%. The total number of cell, the percentage of cells in S and G2/M phase of the cell cycle and the incorporation of 3H-thymidine into DNA were strongly increased in response to FBS, whereas EGF and TPA were without effect. The proliferation was reduced by approximately 50% after pretreatment with PD98059. The results indicate that a persistent ERK activation of a critical size leads to type 2 cell proliferation, and that the proliferative response may also depend on a MEK-independent ERK activation.
Thrane
E V
EV
Department of Environmental Medicine, National Institute of Public Health, Oslo, Norway. vibeke.thrane@folkehelsa.no
Schwarze
P E
PE
Thoresen
G H
GH
Låg
M
M
Refsnes
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M
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005419:Flavonoids / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003470:Culture Media; D004791:Enzyme Inhibitors; D005419:Flavonoids; D004815:Epidermal Growth Factor; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one