[Effect of urotensin II on the airway smooth muscle cell proliferation and its mechanism].
OBJECTIVE
To investigate the effect and mechanism of Urotensin II on the airway smooth muscle cell proliferation.


METHODS
(1) Using 3H-TdR incorporation to determine the effect of Urotensin II on the rat airway smooth muscle cells DNA synthesis. Different inhibitors were used to study the role of different signal transduction pathway such as protein kinase C (PKC), mitogen-activated protein kinase (MAPK), Calcineurin (CaN), Calmodulin-dependent protein kinase (CaM-PK) and calcium channel in the mitogenic effect of Urotensin II on the airway smooth muscle cells. (2) Using Fura-2/AM to measure the effect of Urotensin II on the cytosolic free calcium concentration.


RESULTS
(1) Urotensin II (10(-10)-10(-6) mol/L) increased the airway smooth muscle cell 3H-TdR incorporation in a dose-dependent manner and Urotensin II 10(-6) mol/L reached the maximal effect. It was seven times as high as that of control (P < 0.01). (2) H7, PD98059, and nicardipine, inhibitors of PKC, MAPK and calcium channel, significantly inhibited Urotensin II (10(-7) mol/L)-stimulated airway smooth muscle cell 3H-TdR incorporation, with the inhibitory rate of 29% (P < 0.05), 45% (P < 0.01), and 28% respectively (P < 0.05). W7, an inhibitor of CaM-PK, had no effect (P > 0.05). (3) Cyclosporin A (10(-8)-10(-6) mol/L), inhibitor of CaN, an inhibited the airway smooth muscle cell 3H-TdR incorporation induced by Urotensin II (10(-7) mol/L) in a dose-dependent manner, with the inhibitory rate of 76% at 10(-6) mol/L (P < 0.01). (4) Urotensin II (10(-6) mol/L) promoted cytosolic free calcium concentration increase by 18% (P < 0.01).


CONCLUSIONS
The effect of Urotensin II-stimulated airway smooth muscle cells DNA synthesis is mediated by Ca2+, PKC, MAPK and CaN signal transduction pathway.
Respiratory Department, Third Hospital, Beijing University, Beijing 100083, China.
Y
Y
Chen
M
M
Zhao
C
C
Xia
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014132:Trachea / Q000166:cytology; D014579:Urotensins / Q000494:pharmacology*
D014579:Urotensins; D004247:DNA; C029677:urotensin II