GENE-EXPRESSION OF THE RENIN-ANGIOTENSIN SYSTEM IN HUMAN KIDNEY

Background Immunocytochemical studies have revealed that all component s of the renin-angiotensin system are widely distributed in human tiss ues yet the information on the gene expression of the renin-angiotensi n system in various types of cell remains scarce. Objective We explore d the presence of a local renin-angiotensin system in human kidney. Me thods We sought to determine the presence of messenger RNA (mRNA) enco ding for renin, angiotensinogen, and angiotensin converting enzyme (AC E) in cultured human glomerular cells and human umbilical vein endothe lial cells using a two-step polymerase chain reaction. The gene expres sion of the renin-angiotensin system in normal human kidney and in dis eased kidney was studied by in-situ hybridization using synthetic olig onucleotides. Results By using a two-step polymerase chain reaction, r enin, angiotensinogen, and ACE mRNA were found in cultured mesangial a nd epithelial cells but only ACE mRNA was present in human umbilical v ein endothelial cells. Renin mRNA was detected in juxtaglomerular gran ular cells and also in glomerular and tubular epithelia in normal kidn ey by in-situ hybridization. A similar tubular, but not mesangial, dis tribution was found with angiotensinogen and ACE mRNA. In contrast, st ronger signals for renin, angiotensinogen and ACE mRNA were detected i n mesangial and epithelial cells of kidney tissues from hypertensive p atients and from patients with renal pathology characterized by mesang ial proliferation (immunoglobulin A nephropathy, diabetes mellitus, or lupus nephritis). Conclusions That gene expression of the renin-angio tensin system occurs in resident glomerular cells supports the hypothe sis that there is a local renin-angiotensin system in human kidney. Ou r 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. (C) 1998 Ra pid Science Ltd.