Literature DB >> 12791183

Endothelin-1 promoted proliferation of vascular smooth muscle cell through pathway of extracellular signal-regulated kinase and cyclin D1.

Ying-Min Zhang1, Ke-Qiang Wang, Guo-Min Zhou, Ji Zuo, Jun-Bo Ge.   

Abstract

AIM: To investigate whether endothelin-1 (ET-1) can promote human umbilical artery smooth muscle cell (HUASMC) proliferation through pathway of extracellular signal-regulated kinase (ERK) and cyclin D1.
METHODS: The effects of ET-1 and PD98059 on HUASMC were evaluated by MTT assay. The content of DNA was defined by [3H]TdR assay and cell cycle was analyzed by flow cytomerty. Western blot analysis was employed to detect the active phosphorylated state of ERK and the expression of cylin D1.
RESULTS: Firstly, ET-1 (100 nmol/L) stimulated HUASMC proliferation compared with the group without ET-1 (P<0.05) and PD98059 group (P<0.05). PD98059 inhibited the HUASMC proliferation stimulated by ET-1 (P<0.05). Secondly, ET-1 stimulated DNA synthesis of HUASMC compared with the group without ET-1 (P<0.05). Thirdly, ET-1 promoted the cell cycle transition from G0/G1 phase to S phase. G0/G1 phase cell percentage was obviously decreased compared with the group without ET-1 (P<0.05). S phase cell percentage was increased compared with the group without ET-1 (P<0.05). Fourthly, ET-1 increased the phosphorylated level of ERK and the expression of cylin D1, an inhibitor of ERK blocked phosphorylated level of ERK and cyclin D1 expression. ERK phosphorylated level of ET-1 group was evidently increased compared with PD98059 group (P<0.05), Cyclin D1 protein expression also was increased compared with PD98059 group (P<0.05). While nonphosphorylated ERK expression remained unchanged.
CONCLUSION: Endothelin-1 promoted vascular smooth muscle cell proliferation through pathway of ERK and cyclin D1.

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Year:  2003        PMID: 12791183

Source DB:  PubMed          Journal:  Acta Pharmacol Sin        ISSN: 1671-4083            Impact factor:   6.150


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