Protein expression of factors involved in the development of renal interstitial fibrosis in old SHR

Abstract

In the present work we tested the hypothesis that the increased interstitial fibrosis in juxtamedullary cortex (JMC) of the Spontaneously Hypertensive Rat (SHR) may be due to a disturbance of the balance between synthesis and degradation of collagens. The protein expressions of matrix metalloproteinases (MMP) and their inhibitors, tissue inhibitors of metalloproteinases (TIMP), were therefore measured using immunoblotting. Samples were taken from the JMC and outer cortex (OC) from SHR, and were compared to samples from the Wistar Kyoto (WKY) normotensive controls. The morphology of the JMC in SHR showed focal interstitial fibrosis while OC was normal. Using Sirius red as a marker, increased amount of collagen was found in JMC of SHR. The protein level of MMP-2 was found to be 490.6± 98.0 % in JMC of SHR (Protein level of OC of WKY: 100%), significantly higher than in OC of SHR (p<0.015) and JMC of WKY (p<0.002). MMP-9 was 24.2 ± 3.1 % in JMC of SHR, not statistically different from outer cortex but significantly lower than in JMC of WKY. TIMP-1 was up-regulated in JMC of SHR compared to OC (988.4 ± 280.8 % vs. 480.2 ± 100.9 %, p <0.026). TIMP-2 showed small differences between SHR and WKY. In conclusion, despite an increased MMP-2 expression in JMC of SHR, decreased MMP-9 and increased expression of TIMP-1 favour locally deposition of fibrosis in JMC of SHR. The source of research support was Norwegian Council of Cardiovascular Research