Cook J L, Chen L, Bhandaru S, Bakris G L, Re R N
Alton Ochsner Medical Foundation, New Orleans, Louisiana.
Antisense Res Dev. 1992 Fall;2(3):199-210. doi: 10.1089/ard.1992.2.199.
Local renin-angiotensin systems (RAS) exist in many cell types, and angiotensin II (AII) has growth regulatory effects in some tissues. We demonstrated the presence of angiotensinogen (ANG) mRNA in cultured human mesangial cells (MC) and SHSY-5Y human neuroblastoma cells using reverse transcription and the polymerase chain reaction (RT/PCR) followed by hybridization to a human ANG-specific oligonucleotide probe. We speculated, therefore, that AII might act in an autocrine or paracrine fashion to regulate the growth of mesangial cells and neuroblastoma cells. Sense and antisense oligonucleotides were next synthesized complementary to the ANG transcription start site. Antisense but not sense oligonucleotides decreased [3H]thymidine incorporation into DNA by both MC and neuroblastoma cells. Growth of antisense oligonucleotide-treated cells was restored to control levels by the addition of AII but not by the addition of basic fibroblast growth factor. Neither oligonucleotide affected [3H]thymidine incorporation in mouse L929 cells. These data indicate that locally produced AII can act in an autocrine or paracrine fashion to alter the growth of human mesangial and neuroblastoma cells. Therefore, they suggest a role for local RAS in the pathogenesis of growth abnormalities in the cardiovascular system as well as in some forms of malignancy.
局部肾素 - 血管紧张素系统（RAS）存在于多种细胞类型中，且血管紧张素II（AII）在某些组织中具有生长调节作用。我们运用逆转录和聚合酶链反应（RT/PCR），随后与人类ANG特异性寡核苷酸探针杂交，证实了培养的人系膜细胞（MC）和SHSY - 5Y人神经母细胞瘤细胞中存在血管紧张素原（ANG）mRNA。因此，我们推测AII可能以自分泌或旁分泌方式作用，调节系膜细胞和神经母细胞瘤细胞的生长。接下来合成了与ANG转录起始位点互补的正义和反义寡核苷酸。反义而非正义寡核苷酸降低了MC和神经母细胞瘤细胞将[3H]胸苷掺入DNA的量。添加AII可使经反义寡核苷酸处理的细胞生长恢复至对照水平，而添加碱性成纤维细胞生长因子则不能。两种寡核苷酸均不影响小鼠L929细胞的[3H]胸苷掺入。这些数据表明，局部产生的AII可通过自分泌或旁分泌方式改变人系膜细胞和神经母细胞瘤细胞的生长。因此，它们提示局部RAS在心血管系统生长异常以及某些恶性肿瘤形式的发病机制中发挥作用。
