The Expression And The Possible Role Of Heat Shock Protein 27 In Rats With Tubulointerstitial Injury

Objective: To investigate the expression of heat shock protein 27 (HSP27) in the progression of tubulointerstitial injury in rats with unilatral ureteral obstruction(UUO), and to clarify the possible role of HSP27 in the pathogenesis of ubulointerstitial injury, and to provide new ideas and useful direction for preventing and treating tubulointerstitial injury.Methods: The tubulointerstitial injury models are induced in rats by obstraction of unilateral ureter. The time course of the fibrotic process in rats with UUO was examined, and the expression of HSP27, transforming growth factor-β₁ (TGF-|3|), proliferative cell nuclear antigen(PCNA), and α-smooth muscle actin(α-SMA) in renal tubulointerstitium was observed by immunohistochemistry or by situ hybridization. The correlativity of the expression of HSP27 with the progression of tubulointerstitial injury also was evaluated.Results: (1) Weak expression of HSP27 was found in glomerular epithelial cells and mesangial cells, and mild expression in a few collecting tubules. There was no expression of HSP27 in mesenchyme. However HSP27 mRNA was expressed in all parts above on the cortex regions in control rats. The expression of protein and mRNA-of HSP27 significantly increased in renal tubules on the cortex regions in rats with unilatral ureteral obstruction (UUO) and mainly located in dilated renal tubules. The mesenchymic cells also significantly expressed HSP27mRNA on the cortex regions during the procession of tubulointerstitial injury, but not express the protein. There was a significantly increase in the rates of positive area of HSP27 or the percentages of the positive cells of HSP27 mRNA of renal tubules on the cortex regions in models. At the 3rd day, they came to the peak and then declined with the progression of tubulointerstitial injury, and in accordance with each other(r=0.973,p<0.01). But the percentages of the positive cells of HSP27 mRNA of the glomeruli and mesenchyme had no difference between all of the experimental rats. However, from the 3rd day to the 14th day, either the rates of positive area of HSP27 or the percentages of the positive cells of HSP27 mRNA in the renal tubules had a converse correlation with the tubular injury indexes(TI) in rats with UUO(r=-0.974, P<0.05; r=0.971, p<0.05). (2) The expression of TGF-β₁ in renal tubules obviously increased in all rats with tubulointerstitial injury. The rates of positive area of TGF-β₁, came to the peak at the 7th day and then sustained up to the 14th day. Positive stain of TGF-β₁ mainly located in injurious tubules, including dilated, atrophic and denaturalized tubules. Only a few mesenchymic cells expressed TCP-β₁ on the cortex regions in rats with UUO. In models, the rates of positive area of TGF-β₁ was correlated with tubule injury indexes (r=0.971, P<0.01), and it also had a converse correlation with the rates positive area of HSP27 or the percentages of the positive cells of HSP27 mRNA in the renal tubules on the cortex regions from the 3rd day to the 14th day (r=-0.972, p<0.05, r=-0.986,P<0.05). (3) The expression of PCNA in renal tubules and mesenchymes obviously enhanced in all rats with tubulointerstitial injury at the first day after UUO, and there was a peak for the count of positive cells per field of vision (x200) of PCNA in renal tubules or mesenchyme on the renal cortex regions in models at the 3rd day, then declined with the progression of tubulointerstitial injury. In mesenchyme in rats with UUO, the count of positive cells of PCNA of renal tubules was close to that of the controls at the 10th day, but the count of positive cells of PCNA also was markedly higher than that of controls. The count of positive cells of PCNA had a correlation with the rates of positive area of HSP27 or the percentages of the positive cells of HSP27 mRNA in renal tubules on the cortex regions in models ( r=0.979,P<0.01; r=0.996, P<0.01 ) . (4) Strong positive stains of α-SMA was found in smooth muscle of blood vessels on the renal cortex reg...