Functional cooperation between IK(Ca) and TRPC1 channels regulates serum-induced vascular smooth muscle cell proliferation via mediating Ca(2+) influx and ERK1/2 activation.
Functional cooperation between IK(Ca) and TRPC1 channels regulates serum-induced vascular smooth muscle cell proliferation via mediating Ca(2+) influx and ERK1/2 activation.
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IKCa 和 TRPC1 通道之间的功能合作通过介导 Ca2 内流和 ERK1/2 激活调节血清诱导的血管平滑肌细胞增殖
DOI：
10.1111/cpr.13385
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发表时间：
2023-04
影响因子：
8.5
通讯作者：
中科院分区：
文献类型：
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作者：
血管平滑肌细胞（VSMC）增殖增加有助于血管疾病的发病机制。中电导钙激活钾（IKCa）通道通过升高细胞内钙离子浓度（[Ca 2 +]i）在VSMC增殖中起重要作用，但其机制尚不清楚。在这里，我们研究了IKCa和瞬时受体电位典型1（TRPC 1）通道在介导细胞外Ca 2+内流中的合作，这反过来又激活了下游Ca 2+信号转导，从而使用血清诱导的细胞增殖模型调节VSMC增殖。血清诱导的细胞增殖伴随IKCa表达上调和[Ca 2 +]i增加。血清诱导的细胞增殖和[Ca 2 +]i的增加被TRAM-34或IKCa敲低的IKCa抑制所抑制。血清诱导的细胞增殖通过用EGTA去除细胞外Ca 2+或用BAPTA-AM去除细胞内Ca 2+以及另外通过TRPC 1敲低而强烈降低。此外，TRPC 1敲低可减弱血清或IKCa激活1-EBIO诱导的[Ca 2 +]i增加。最后，血清诱导ERK 1/2活化，其通过用TRAM-34或BAPTA-AM处理以及TRPC 1敲低而减弱。因此，用PD 98059抑制ERK 1/2抑制血清诱导的细胞增殖。综上所述，这些结果表明IKCa和TRPC 1通道在介导Ca 2+内流中合作，从而激活ERK 1/2通路以促进细胞增殖，从而为VSMC增殖提供新的机制见解。血清诱导VSMC增殖的拟定机制的示意图总结。IKCa和TRPC 1通道协同介导Ca 2+内流和[Ca 2 +]i增加，[Ca 2 +]i增加反过来激活ERK通路，从而刺激VSMC增殖。
The increased proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of vascular diseases. The intermediate conductance calcium‐activated potassium (IKCa) channel plays a critical role in VSMC proliferation by raising the intracellular calcium concentration ([Ca2+]i), but the underlying mechanism is still not unclear. Here we investigated the cooperation between IKCa and transient receptor potential canonical 1 (TRPC1) channels in mediating extracellular Ca2+ entry, which in turn activates downstream Ca2+ signalling in the regulation of VSMC proliferation using serum‐induced cell proliferation model. Serum‐induced cell proliferation was accompanied with up‐regulation of IKCa expression and an increase in [Ca2+]i. Serum‐induced cell proliferation and increase in [Ca2+]i were suppressed by IKCa inhibition with TRAM‐34 or IKCa knockdown. Serum‐induced cell proliferation was strongly reduced by the removal of extracellular Ca2+ with EGTA or intracellular Ca2+ with BAPTA‐AM and, additionally, by TRPC1 knockdown. Moreover, the increase in [Ca2+]i induced by serum or by IKCa activation with 1‐EBIO was attenuated by TRPC1 knockdown. Finally, serum induced ERK1/2 activation, which was attenuated by treatment with TRAM‐34 or BAPTA‐AM, as well as TRPC1 knockdown. Consistently, serum‐induced cell proliferation was suppressed by ERK1/2 inhibition with PD98059. Taken together, these results suggest that the IKCa and TRPC1 channels cooperate in mediating Ca2+ influx that activates the ERK1/2 pathway to promote cell proliferation, thus providing new mechanistic insights into VSMC proliferation. Schematic summary of proposed mechanisms for serum‐induced VSMC proliferation. The IKCa and TRPC1 channels cooperate to mediate Ca2+ influx and an increase in [Ca2+]i that in turn activates the ERK pathway and thereby stimulates VSMC proliferation.
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影响因子：
5.6
作者：
Martín-Bórnez M;Galeano-Otero I;Del Toro R;Smani T
通讯作者：
Smani T
DOI：
10.1152/ajpheart.00355.2010
发表时间：
2011-08-01
影响因子：
4.8
作者：
Espinosa-Tanguma, Ricardo;O'Neil, Caroline;Sims, Stephen M.
通讯作者：
Sims, Stephen M.
影响因子：
5.5
作者：
Bergdahl, A;Gomez, MF;Hellstrand, P
通讯作者：
Hellstrand, P
影响因子：
37.8
作者：
Köhler, R;Wulff, H;Hoyer, J
通讯作者：
Hoyer, J
钙依赖性离子通道和小动脉肌原张力的调节。
影响因子：
4
作者：
Jackson WF
通讯作者：
Jackson WF