AngII-induced glomerular mesangial cell proliferation inhibited by losartan via changes in intracellular calcium ion concentration.
AngII-induced glomerular mesangial cell proliferation inhibited by losartan via changes in intracellular calcium ion concentration.
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DOI：
10.1007/s10238-013-0232-y
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发表时间：
2014-05
影响因子：
4.6
通讯作者：
Ji, Zequan
中科院分区：
文献类型：
--
作者：
Qiu, Guoying;Ji, Zequan
本研究探讨了血管紧张素II（AngII）诱导肾小球系膜细胞（GMC）增殖过程中细胞内[Ca2+]i（细胞内钙离子浓度）和TRPC6（瞬时受体电位通道6）表达的变化，以及氯沙坦的抑制作用。将GMC培养物分为四组，处理24小时：N组（空白对照组）、A组（10 - 7 mol/L AngII）、LT组（10 - 7 mol/L AngII和10 - 5 mol/L氯沙坦）以及Pred组（10 - 7 mol/L AngII和10 - 5 mol/L泼尼松）。通过MTT法和台盼蓝染色法检测GMC的增殖情况。通过免疫荧光监测TRPC6的分布，通过RT - PCR和蛋白质印迹法检测TRPC6的表达，通过激光扫描共聚焦显微镜测量[Ca2+]i。结果表明，用10 - 7 mol/L AngII处理24小时可诱导GMC最大程度的增殖。在A组中，TRPC6在细胞膜上分布不均匀，细胞质内该蛋白的积聚增加，TRPC6和[Ca2+]i表达的增加与细胞增殖一致。在LT组中，氯沙坦显著抑制GMC的增殖，TRPC6和[Ca2+]i水平降低，TRPC6的分布得到改善。泼尼松也显著抑制GMC的增殖，且对Pred组中TRPC6和[Ca2+]i的表达无影响。这些发现表明，AngII可增强TRPC6的表达，增加[Ca2+]i，并与GMC的增殖呈现时间 - 剂量 - 反应关系，而氯沙坦可逆转AngII对GMC增殖的作用。
This study investigated the changes in intracellular [Ca2+]i (intracellular calcium ion concentration) and TRPC6 (transient receptor potential channel 6) expression during angiotensin II (AngII)-induced glomerular mesangial cell (GMC) proliferation, as well as the inhibitory effect of losartan. GMC cultures were split into four groups treated for 24 h: Group N (blank control group), Group A (10−7 mol/L AngII), Group LT (10−7 mol/L AngII and 10−5 mol/L losartan), and Group Pred (10−7 mol/L AngII and 10−5 mol/L prednisone). GMCs proliferation was measured by the MTT and trypan blue assays. The distribution of TRPC6 was monitored by immunofluorescence, the expression of TRPC6 was detected by RT-PCR and Western blotting, and [Ca2+]i was measured by laser scanning confocal microscopy. The results showed that the maximal proliferation of GMCs was induced by treatment with 10−7 mol/L AngII for 24 h. In Group A, the distribution of TRPC6 was not uniform in the cell membrane, there was increased accumulation of this protein within the cytoplasm, and the increased expression of TRPC6 and [Ca2+]i was consistent with the proliferation of cells. In Group LT, losartan inhibited the proliferation of GMCs significantly, the levels of TRPC6 and [Ca2+]i were diminished, and the distribution of TRPC6 was improved. Prednisone also significantly inhibited the proliferation of GMCs and had no effects on the expression of TRPC6 and [Ca2+]i in Group Pred. These findings suggested that AngII could enhance the expression of TRPC6, increase [Ca2+]i, and demonstrate a time–dose–response relationship with the proliferation of GMCs, while losartan reversed the effect of AngII on GMC proliferation.
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影响因子：
30.8
作者：
Reiser, J;Polu, KR;Pollak, MR
通讯作者：
Pollak, MR
影响因子：
56.9
作者：
Winn, MP;Conlon, PJ;Rosenberg, PB
通讯作者：
Rosenberg, PB
影响因子：
13.6
作者：
Eckel, Jason;Lavin, Peter J.;Winn, Michelle P.
通讯作者：
Winn, Michelle P.
影响因子：
5.5
作者：
Shi, J.;Ju, M.;Large, W. A.
通讯作者：
Large, W. A.
DOI：
10.1073/pnas.0813346106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Liao, Yanhong;Plummer, Nicholas W.;Birnbaumer, Lutz
通讯作者：
Birnbaumer, Lutz