Lai K N, Leung J C, Lai K B, To W Y, Yeung V T, Lai F M
Department of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong.
J Hypertens. 1998 Jan;16(1):91-102. doi: 10.1097/00004872-199816010-00014.
Immunocytochemical studies have revealed that all components of the renin-angiotensin system are widely distributed in human tissues yet the information on the gene expression of the renin-angiotensin system in various types of cell remains scarce.
We explored the presence of a local renin-angiotensin system in human kidney.
We sought to determine the presence of messenger RNA (mRNA) encoding for renin, angiotensinogen, and angiotensin converting enzyme (ACE) in cultured human glomerular cells and human umbilical vein endothelial cells using a two-step polymerase chain reaction. The gene expression of the renin-angiotensin system in normal human kidney and in diseased kidney was studied by in-situ hybridization using synthetic oligonucleotides.
By using a two-step polymerase chain reaction, renin, angiotensinogen, and ACE mRNA were found in cultured mesangial and epithelial cells but only ACE mRNA was present in human umbilical vein endothelial cells. Renin mRNA was detected in juxtaglomerular granular cells and also in glomerular and tubular epithelia in normal kidney by in-situ hybridization. A similar tubular, but not mesangial, distribution was found with angiotensinogen and ACE mRNA. In contrast, stronger signals for renin, angiotensinogen and ACE mRNA were detected in mesangial and epithelial cells of kidney tissues from hypertensive patients and from patients with renal pathology characterized by mesangial proliferation (immunoglobulin A nephropathy, diabetes mellitus, or lupus nephritis).
That gene expression of the renin-angiotensin system occurs in resident glomerular cells supports the hypothesis that there is a local renin-angiotensin system in human kidney. Our findings support the previous speculation that the renin-angiotensin system could be a local factor involved in the progression of chronic renal failure and consequent development of hypertension.
免疫细胞化学研究表明，肾素-血管紧张素系统的所有成分广泛分布于人体组织中，但关于肾素-血管紧张素系统在各类细胞中的基因表达信息仍然匮乏。
我们探究了人肾脏中局部肾素-血管紧张素系统的存在情况。
我们试图通过两步聚合酶链反应来确定培养的人肾小球细胞和人脐静脉内皮细胞中编码肾素、血管紧张素原和血管紧张素转换酶（ACE）的信使核糖核酸（mRNA）的存在情况。使用合成寡核苷酸通过原位杂交研究正常人和患病肾脏中肾素-血管紧张素系统的基因表达。
通过两步聚合酶链反应，在培养的系膜细胞和上皮细胞中发现了肾素、血管紧张素原和ACE mRNA，但人脐静脉内皮细胞中仅存在ACE mRNA。通过原位杂交在正常肾脏的球旁颗粒细胞以及肾小球和肾小管上皮细胞中检测到肾素mRNA。血管紧张素原和ACE mRNA在肾小管中呈类似分布，但在系膜中未发现。相比之下，在高血压患者以及以系膜增生为特征的肾脏疾病（免疫球蛋白A肾病、糖尿病或狼疮性肾炎）患者的肾脏组织的系膜细胞和上皮细胞中检测到肾素、血管紧张素原和ACE mRNA的信号更强。
肾素-血管紧张素系统的基因表达发生在驻留的肾小球细胞中，这支持了人肾脏中存在局部肾素-血管紧张素系统的假说。我们的研究结果支持了先前的推测，即肾素-血管紧张素系统可能是参与慢性肾衰竭进展及随后高血压发生的局部因素。
