EXPRESSION OF AMINOPEPTIDASE-A, AN ANGIOTENSINASE, IN GLOMERULAR MESANGIAL CELLS

Glomerular mesangial cells are known to express angiotensin II type 1 receptors and contract in response to circulating and/or locally produ ced angiotensin II. In addition, stimulation of mesangial cell matrix protein synthesis by elevated levels of angiotensin II is known to con tribute to the development of glomerulosclerosis. Previously, we repor ted that mesangial cells were positively immunostained with antiserum directed against aminopeptidase A, the principal angiotensinase in the metabolism of angiotensin II. Here we demonstrate directly that amino peptidase A is expressed in mesangial cells cultured from rat kidney. First, cultured mesangial cells had measurable aminopeptidase A enzyma tic activity. Second, immunoblots for aminopeptidase A were positive f or isolated glomeruli and mesangial cells, although two bands were see n for mesangial cells (approximate to 138 and 144 kD), and only the la rger band was seen for isolated glomeruli and kidney. Third, Northern blot hybridizations of total RNA from mesangial cells or kidney were p ositive and labeled similarly sized bands. Fourth, reverse transcripti on-polymerase chain reaction amplification of mesangial cell total RNA yielded a partial cDNA of the expected size that was confirmed by seq uencing to be identical to rat kidney aminopeptidase A. These results indicate that aminopeptidase A is expressed within mesangial cells. Th ese results further suggest that metabolism of angiotensin II by amino peptidase A could play a protective role in minimizing the adverse eff ects of angiotensin II stimulation of mesangial cells.