Expression Of CD44 In Glomerulosclerosis And Tubulointerstitial Injury In Rat

Objective: The purpose of this study was to observe the temporal and spatial changes of CD44 expression in glomerulosclerosis induced by daunomycin and tubulointerstitial injury caused by unilateral ureteral obstraction (UUO) in rat, to clarify the possible role of CD44 in the pathogenesis of progressive glomerulosclerosis and tubulointerstitial injury, and to provide useful message and means of preventing and treating glomerulosclerosis and tubulointerstitial injury.Methods: Daunomycin was used to induce glomerulosclerosis, and unilateral ureteral was obstracted to cause tubulointerstitial injury in rats. Immunohistochemistry, in situ hybridization and colour pathological image analysis system were used to evaluate the expression of CD44 in these two models, and to analyse the relationship between the level of CD44 expression and the degree pathological lesions of glomerulosclerosis and tubulointerstitial injury at different time.Results: (1) There was an obvious increase of CD44 mRNA expression (1st week) and protein expression (2nd week) in some inherent cells in glomerulus. They were also observed in areas of blood capillary dent and in tubular epithelial cells arround glomerulus at 3rd week, and in capillary epithelial cells adhere to Bowman's capsule at 4th week. Following the progression of glomerulosclerosis, the most striking increase of CD44 protein and mRNA expression were shown in sclerosing glomerulus. CD44 positive area per cell and the percentage of CD44 mRNA positive cells in glomerulus were also increased in progressive glomerulosclerosis, which were correlatedpositively with glomerular sclerosis index (r1=0.754, p<0.01; r2=0.744, p<0.01). (2) Tubular epithelial cells express strongly CD44 protein and mRNA on day 3 after UUO. There was a dramatic increase of CD44 expression in tubules, which were atrophy or dilatation. Furthermore, inflammatory cells with CD44 expression were seen in interstitial area. During the disease development, CD44 positive area and the number of CD44 mRNA positive cells in per tubulointerstitial area were also increased in progressive tubulointerstitial injury. They were correlated strongly with tubulointerstitial injury index (r1=0.815, p<0.01;r2=0.854,p<0.01).Conclusions: (1) CD44 may participate in accelerated glomerulosclerosis and progressive tubulointerstitial injury. (2) The level of CD44 expression may be regard as a reference index, which was used to determine the degree pathological lesions in glomerulosclerosis and tubulointerstitial injury.