Valsartan On Mesangial Cell Proliferation In Rat Anti-thy1 Antibody

The proliferation of mesangial cells(MC) is a common pathological feature of many glomerular diseases such as mesangial proliferative glomerulonephritis, lupus nephritis, JgA and diabete nephropathy which often progress to glomerular sclerosis. So it is very important to investigate the mechanism of the proliferation of MC. In the past few years the relationship between cell-cycle regulatory proteins and the proliferation of glomerular intrinsic cells has been documented in focus. It was found that CDK2, one of the important positive cell-cycle regulatory proteins, and p27, one of the negative cell-cycle regulatory proteins, play important roles in the proliferation of intrinsic glomerular cells. It was also found that Angiotensin II is involved in the onset and progression of many renal diseases by exerting growth promoting effects on the kidney in vivo, and it stimulates the proliferation of glomerular endothelial and mesangial cells in vitro. The relationship between p27 and Angiotensin II has been noted in the study of hypertrophy of cultured LLC-PK1 cells. It was reported that ACEIs showed their renoprotective benefits of anti-proliferation. However, the expression of cell-cycle regulatory proteins has not been discussed in the glomerulus to explore the mechanism of ACEI's renoprotective effects. The purpose of this study is to determine the renoprotective benefits and to explore the mechanism about cell-cycle regulation of valsartan, a non-peptide angiotensin 1 type recepter antagonist, in the rats with Thyl nephritis. In detail, we administrated of valsartan to rats with Thyl glomerularnephritis to examine its effects on the clinical features and the proliferation of MC in vivo. Meanwhile immunohistochemistry and Western blot were used to detect the expression of PCNA, CDK2 and p27 in glomerulus. The results obtained were as follows: (1) The proteinuria was significantly reduced in the valsartan-treated nephritic rats than in the untreated rats at day 3 to 7 of Thy 1 nephritis. While no change was noted in mean systemic blood pressure, BUN and SCr in all rats. (2) Glomerular hypercellularity and mesangial matrix expansion was found at day 3 of Thyl both in treated and untreated rats. And it was more obvious at day 5 and 7 of the disease. However, both the total glomerular cells and expansion of mesangial matrix were significantly reduced in valsartan-treated rats. (3) PCNA and CDK2 have very low levels of expression in the normal rat glomerulus in immunohistochemistry and Western blot, while p27 has high expression. At day 3 to 7 of Thy 1, there was an increase in PCNA and CDK2 expression, accompanied with a decrease in p27 expression. In the valsartan-treated rats, the levels of PCNA and CDK2 in glomerulus were down-regulated at day 3 to 7 versus untreated nephritic rats while the level of p27 was up-regulated. These results suggest: The high expression of p27 plays a critical role in maintaining quiescence in mesangial cells. The proliferation of mesangial cells is associated with the down-regulation of p27 level and up-regulation of CDK2. Administration of valsartan to rats with mesangial proliferative glomerulonephritis can decrease proteinuria and renal morphological lesIons partly. The renoprotective effects of Valsartan on rats with Thvl nephritis, is partly through maintaining the high expression of p27 and inhibiting the expression of CDK2 in mesangial cells and therefore ameliorating mesangial cells proliferation. This experimental study maybe provide...