Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells.
Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells.
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多囊这杆-1在通过肾细胞中钙振荡调节细胞增殖中的新作用。
DOI：
10.1111/j.1365-2184.2008.00529.x
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发表时间：
2008-06
影响因子：
8.5
通讯作者：
del Senno L
中科院分区：
文献类型：
--
作者：
Aguiari G;Trimi V;Bogo M;Mangolini A;Szabadkai G;Pinton P;Witzgall R;Harris PC;Borea PA;Rizzuto R;del Senno L
Abstract. Objectives:多囊蛋白-1（PC 1）是一种调节Ca 2+渗透性阳离子通道的信号受体，在常染色体显性遗传性多囊肾病中发生突变，其典型特征是细胞增殖增加。然而，PC 1对Ca 2+稳态、信号传导和细胞增殖起作用的确切机制仍不清楚。在这里，我们研究了PC 1作为非电容性Ca 2+进入（NCCE）和Ca 2+振荡的调节剂的可能作用，以及对细胞增殖的下游影响。结果和讨论：通过使用RNA干扰，我们表明HEK 293细胞中内源性PC 1的缺失导致血清诱导的Ca 2+振荡增加，触发活化T细胞活化的核因子并导致细胞周期进展。同样，在PC 1突变的肾囊细胞系中，Ca 2+振荡和细胞增殖增加，但在外源表达PC 1的细胞中，这两种异常特征都减少。值得注意的是，NCCE途径的阻断剂，但不是CCE的阻断剂，钝化异常振荡和细胞增殖。因此，我们的研究首次证明PC 1调节Ca 2+振荡，并提供了解释常染色体显性多囊肾病中异常Ca 2+稳态与细胞增殖之间关系的分子机制。
Abstract. Objectives: Polycystin‐1 (PC1), a signalling receptor regulating Ca2+‐permeable cation channels, is mutated in autosomal dominant polycystic kidney disease, which is typically characterized by increased cell proliferation. However, the precise mechanisms by which PC1 functions on Ca2+ homeostasis, signalling and cell proliferation remain unclear. Here, we investigated the possible role of PC1 as a modulator of non‐capacitative Ca2+ entry (NCCE) and Ca2+ oscillations, with downstream effects on cell proliferation. Results and discussion: By employing RNA interference, we show that depletion of endogenous PC1 in HEK293 cells leads to an increase in serum‐induced Ca2+ oscillations, triggering nuclear factor of activated T cell activation and leading to cell cycle progression. Consistently, Ca2+ oscillations and cell proliferation are increased in PC1‐mutated kidney cystic cell lines, but both abnormal features are reduced in cells that exogenously express PC1. Notably, blockers of the NCCE pathway, but not of the CCE, blunt abnormal oscillation and cell proliferation. Our study therefore provides the first demonstration that PC1 modulates Ca2+ oscillations and a molecular mechanism to explain the association between abnormal Ca2+ homeostasis and cell proliferation in autosomal dominant polycystic kidney disease.
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影响因子：
21.3
作者：
Li, XG;Luo, Y;Zhou, J
通讯作者：
Zhou, J
影响因子：
56.9
作者：
Mochizuki, T;Wu, GQ;Somlo, S
通讯作者：
Somlo, S
影响因子：
4
作者：
Berridge, MJ
通讯作者：
Berridge, MJ
影响因子：
4.8
作者：
Grimm, DH;Cai, YQ;Caplan, MJ
通讯作者：
Caplan, MJ
影响因子：
5.2
作者：
Kim, H;Bae, Y;Kang, SM
通讯作者：
Kang, SM