Expression of extracellular matrix components and transforming growth factor-β1 in kidneys of spontaneously hypertensive rats before the development of hypertension.

Several lines of evidence suggest that renal mechanisms play a major role in the pathogenesis of primary hypertension, and this is well documented in the spontaneously hypertensive rat (SHR). To identify kidney biosynthetic abnormalities that precede the onset of hypertension, we studied the expression of fibronectin (FN), collagen IV, and transforming growth factor-β1 (TGF-β1) in young SHR (4 weeks of age) whose systolic blood pressure was normal and similar to that of age-matched control Wistar Kyoto rats (WKY). In three independent experiments glomeruli were isolated from SHR and WKY (5-8 rats in each group), RNA extracted, and mRNA levels studied by Northern analysis. In SHR glomeruli FN and collagen IV mRNA levels were decreased by 2.5- and 1.5-fold, respectively, when compared to levels in the WKY glomeruli. In contrast, the expression of TGFβ1 in glomeruli from SHR was 1.7-fold greater than in WKY, and β-actin mRNA levels were unchanged. These abnormalities were maintained in vitro since the expression of FN and collagen IV were decreased by 3.1 and 1.8-fold, respectively, in cultured mesangial cells from SHR. In addition, mesangial cells from SHR showed a higher growth rate than those from WKY. In summary, before the development of hypertension SHR displayed decreased expression of FN and collagen IV with upregulation of TGFβ1 in isolated glomeruli and cultured mesangial cells, together with higher growth rate in the latter cells. These abnormalities appear to reflect genetic characteristics, and should be studied vis à vis a contribution to the pathogenesis of hypertension.