Gene expression of the renin-angiotensin system in human kidney

Abstract

Background. 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. Objective. We explored the presence of a local renin-angiotensin system in human kidney. Methods. 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. Results. 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). Conclusions. 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.