Store-operated Ca entry regulates the cardiac hypertrophic response

钙进入心脏肥大反应的重要性是有据可查的，但实际的钙进入渠道仍然未知。瞬时受体电位（TRP）蛋白被认为形成参与各种细胞增殖的Ca进入通道。本研究的目的是探讨TRP通道在心肌肥厚发生发展中的可能作用。EMSA显示NRSF（神经元限制性沉默因子）和TRPC 1基因组DNA中的NRSE样序列之间的相互作用。我们发现TRPC 1在dnNRSF-Tg小鼠心脏中表达上调，这与扩张型心肌病相似。提示TRPC 1具有胎儿心脏基因的特征，在心肌病中有重表达。虽然TRP C1，C3，C5和C6的组成性表达，只有TRPC 1的表达显着增加，在腹部结扎大鼠的心脏相比，假手术大鼠。使用新生大鼠心肌细胞的原代培养物，我们检测到心肌细胞的增殖， ...更多信息 在内皮素-1（ET-1）治疗后，TRPC 1、脑钠肽（BNP）和心钠素（ANF）的表达，以及钙池操作的钙内流（SOCE）和细胞表面积的增加。通过小干扰RNA（siRNA）沉默TRPC 1基因可减弱SOCE并防止ET-1、血管紧张素II（AT II）和苯丙氨酸（PE）诱导的心肌肥大。在HEK 293 T细胞中，TRPC 1过表达增强SOCE，导致活化T细胞核因子（NFAT）启动子活性增加，而与显性阴性形式的TRPC 1共转染抑制它。我们证明了血管紧张素II和随后的NF-κ B激活通过增强TRPC 1表达诱导hCASMC肥大。总之，TRPC 1在Ca内流中起作用，并且其上调参与心脏和血管肥大的发展;此外，它在控制心脏和血管肥大的信号通路的调节中起重要作用。少

The importance of Ca entry in the cardiac hypertrophic response is well documented, but the actual Ca entry channels remain unknown. Transient receptor potential (TRP) proteins are thought to form Ca entry channels that are involved in the proliferation various cells. The purpose of this study was to explore the potential involvement of TRP channels in the development of cardiac hypertrophy. EMSA revealed an interaction between NRSF (neuron restrictive silence factor) and a NRSE-like sequence in TRPC1 genomic DNA. We found that TRPC1 was up-regulated in dnNRSF-Tg mice heart which mimick dilated cardiomyopathy. These results suggest that TRPC1 has the character of fetal cardiac gene and reexpresses in the cardiomyopathy. Although TRPs C1, C3, C5, and C6 were constitutively expressed, only TRPC1 expression was significantly increased in the hearts of abdominal aortic-banded rats compared to sham-operated rats. Using primary cultures of neonatal rat cardiomyocytes, we detected increases i … More n the expression of TRPC1, brain natriuretic peptide (BNP), and atrial natriuretic factor (ANF), as well as increases in store-operated Ca entry (SOCE) and cell surface area, following endothelin-1 (ET-1) treatment. Silencing of the TRPC1 gene via small interfering RNA (siRNA) attenuated SOCE and prevented ET-1-, angiotensin-II (AT II)-, and phenylephrine (PE)-induced cardiac hypertrophy. In HEK 293T cells, overexpression of TRPC1 augmented SOCE, leading to an increase in nuclear factor of activated T cells (NFAT) promoter activity, while co-transfection with dominant-negative forms of TRPC1 suppressed it. Mreover, we examined the involvement of TRPC1 in the vascular smooth muscle cell hypertrophy. We demonstrate Ang II and subsequent NF-kappaB activation induces hCASMC hypertrophy through an enhancement of TRPC1 expression. In conclusion, TRPC1 functions in Ca influx, and its upregulation is involved in the development of cardiac and vascular hypertrophy ; moreover, it plays an important role in the regulation of the signaling pathways that govern cardiac and vascular hypertrophy. Less