Expression Of HSP47 In The Renal Tubulointerstital Fibrosis And The Regulation Of Valsartan

Objective: Heat shock protein 47(HSP47) is a collagen-specific molecular chaperone localized in the endoplasmic reticulum(ER) of the collagen producing cells.HSP47 takes part in the modification, processing and secretion of collagen, plays an important role during the biosynthesis of collagen molecules and progression of fibrosis. Inhibition of HSP47 expression can suppress collagen accumulation and attenuate the histologic manifestations of the fibrosis. By the observation of the expression HSP47mRNA and the effect of valsartan, an angiotensin II receptor antagonist, on the expression of HSP47mRNA in the unilateral ureteral obstruction (UUO) rats, this study aimed to investigate the possible role of HSP47 in the progression of the tubulointerstitial fibrosis and the effect of renin-angiotensin system(RAS) on HSP47 expression. Identification of the molecular mechanism of HSP47 induction during UUO may give an insight into the novel aspects of the molecular pathophysicology of interstitial fibrosis.Methods: Thirty-six female sprague-dawley rats,weighting 250-300g, were used. The rats were randomly divided into shame operation group(group A), UUO model group(group B) and UUO model treated with valsartan (10mg.kg~1.d~1)group(group C). Rats were killed and the kidneys were removed after ten days of the operation. Tissues were processed to paraffic sections and stained with HE, PAS and picrosirius. The relative volume of the interstitium of the cortex was determined on the sections stained by the PAS method. The expression of collagen I , a -smooth muscle actin ( a -SMA) and transforming growth factor- & i(TGF P i) were examined by immnohistochemistry. The expressions of HSP47mRNA and TGFP ImRNA were examined by reverse transcription polymerase chain reaction(RT-PCR).Results: The kidneys of group B show markedly expanded interstitium and cellular infiltration. The kidneys of group C had a modest expansion of interstitium and cellular infiltration. The relative volume of the interstitium of the cortex were higher in both group B and C than in group A(P<0.01), and it was lower in group C than in group B(P<0.01). The expressions of collagen I , a -SMA and TGF P , in the group B and C than in the group A(P<0.01), but they were lower in group C than in group B(P<0.01). Collagen I immunoreactivity was observed in the periglomerular and peritubular interstitium of the obstructed kidneys and the distribution of a -SMA was similar to the collage I distribution pattern. The positive signal of TGF P jwas mainly located inthe tubular cells on the juxtamedually regions. The expression of HSP47mRNA and TGF 0 , mRNA were significantly increased in group B and C than in the group A(P<0.01), at the same time, it was decreased in group C than in group B(P<0.01).Conclusion: These result demonstrate the up regulation of HSP47 during the progression of interstitial fibrosis, and suggest the potential role of HSP47 in the pathogenesis of interstitial fibrosis. Renin-angiotensis system may induce the expression of HSP47 and implicate in the pathogenesis of interstitial fibrosis. Valsartan could suppress the expression and, reduce the accumulation of collagen and ameliorate the fibrotic changes of the interstitium.