Growth factors and extracellular signal-regulated kinase in vascular smooth muscle cells of normotensive and spontaneously hypertensive rats.
OBJECTIVE
Transforming growth factor-beta1 (TGF-beta1) stimulates vascular smooth muscle cell growth in spontaneously hypertensive rats (SHR), but inhibits cell growth in normotensive Wistar- Kyoto (WKY) rats. The present study was undertaken to test the hypothesis that TGF-beta1 might differentially modulate the activities of mitogen-activated protein (MAP) kinase family members (ERK, JNK and p38) in vascular smooth muscle cells of SHR and WKY rats.


METHODS
MAP kinase activity was measured from cultured vascular smooth muscle cells in response to TGF-1 by specific substrate phosphorylation of myelin basic protein, GST-c-Jun and GST-ATF2.


RESULTS
Exposure of cultured vascular smooth muscle cells from SHR or WKY rats to TGF-beta1 resulted in a marked increase in the activity of ERK, but not of JNK or p38. The increase of ERK activity stimulated by TGF-beta1 appeared similar in time course and extent in both WKY and SHR cells, with increased activity peaking at 15 min of incubation. Epidermal growth factor (EGF) also stimulated the activity of ERK, in both WKY and SHR cells, but nor of JNK or p38, with stimulation of ERK activity by EGF occurring more rapidly in SHR cells than in those from WKY rats. Co-incubation of SHR cells with TGF-beta1 and EGF showed additive effect on ERK activity.


CONCLUSIONS
The results provide the first evidence that TGF-beta1 activates ERK in vascular smooth muscle cells of both normotensive and hypertensive rats. The matching response of ERK activation to TGF-1 in SHR cells suggests that the MAP kinase-signaling pathway remains largely unchanged in the regulation of vascular smooth muscle growth by TGF-1 in spontaneously hypertensive rats.
Ebisui
O
O
Baker Medical Research Institute, Prahran, Victoria, Australia.
Dilley
R J
RJ
Li
H
H
Funder
J W
JW
Liu
J P
JP
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3; D006133:Growth Substances / Q000502:physiology*; D006973:Hypertension / Q000201:enzymology*; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D006133:Growth Substances; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3