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The signal transduction pathway in the proliferation of airway smooth muscle cells induced by urotensin Ⅱ
作者姓名:Chen YH  Zhao MW  Yao WZ  Pang YZ  Tang CS
作者单位:Department of Respiratory Disease,Third Hospital,Peking University,Department of Respiratory Disease,Third Hospital,Peking University,Department of Respiratory Disease,Third Hospital,Peking University,Institute of Cardiovascular Research,First Teaching Hospital,Peking University,Institute of Cardiovascular Research,First Teaching Hospital,Peking University Beijing 100083,China,Beijing 100083,China,Beijing 100083,China,Beijing 100034,China,Beijing 100034,China
基金项目:ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 3 0 3 0 0 14 3 )andtheNationalEducationCommitteeDoctoralFoundation (No 960 2 40 47)
摘    要:Background Human urotensin Ⅱ (UⅡ) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that UⅡ is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of UⅡ mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by UⅡ. Methods In primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CaN) induced by UⅡ were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by UⅡ was measured using Fura-2/AM. Results UⅡ 10-7 mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P<0.01), respectively, after incubating for 20 minutes. It increased CaN activity in a time-dependent manner, being 1.68 times as that of control for 24 hours (P<0.01). It promoted the cytosolic free calcium concentration increase of 18% (P<0.01). CsA 10-6 mol/L and H7 50 μmol/L inhibited UⅡ-stimulated CaN activity by 45% (P<0.01) and 21% (P<0.05), respectively, while PD98059 50 μmol/L had no effect on CaN activity (P>0.05). CsA 10-6 mol/L inhibited UⅡ-stimulated PKC activity by 14% (P<0.05), while having no effect on MAPK activity (P>0.05). Conclusions UⅡ increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The signal transduction pathway between PKC and CaN has cross-talk.

关 键 词:尾加压素Ⅱ  信号转导途径  细胞增殖  气道平滑肌细胞  血管收缩剂  蛋白激酶

The signal transduction pathway in the proliferation of airway smooth muscle cells induced by urotensin II
Chen YH,Zhao MW,Yao WZ,Pang YZ,Tang CS.The signal transduction pathway in the proliferation of airway smooth muscle cells induced by urotensin II[J].Chinese Medical Journal,2004,117(1):37-41.
Authors:Chen Ya-hong  Zhao Ming-wu  Yao Wan-zhen  Pang Yong-zheng  Tang Chao-shu
Institution:1. Department of Respiratory Disease, Third Hospital, Peking University, Beijing 100083, China
2. Institute of Cardiovascular Research, First Teaching Hospital, Peking University, Beijing 100034, China
Abstract:BACKGROUND: Human urotensin II (UII) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that UII is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of UII mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by UII. METHODS: In primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CaN) induced by UII were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by UII was measured using Fura-2/AM. RESULTS: UII 10(-7) mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P < 0.01), respectively, after incubating for 20 minutes. It increased CaN activity in a time-dependent manner, being 1.68 times as that of control for 24 hours (P < 0.01). It promoted the cytosolic free calcium concentration increase of 18% (P < 0.01). CsA 10(-6) mol/L and H7 50 micromol/L inhibited UII-stimulated CaN activity by 45% (P < 0.01) and 21% (P < 0.05), respectively, while PD98059 50 micromol/L had no effect on CaN activity (P > 0.05). CsA 10(-6) mol/L inhibited UII-stimulated PKC activity by 14% (P < 0.05), while having no effect on MAPK activity (P > 0.05). CONCLUSIONS: UII increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The signal transduction pathway between PKC and CaN has cross-talk.
Keywords:urotensin Ⅱ  airway smooth muscle cells  protein kinase C  mitogen-activated protein kinase  calcineurin
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