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- W2137169969 abstract "ABSTRACT. Tubulointerstitial fibrosis is considered to be common endpoint result of many forms of chronic renal diseases. Except for renal replacement, chronic renal fibrosis is presently incurable. This study demonstrates that the combination of hepatocyte growth factor (HGF) gene therapy with inhibition of the renin-angiotensin system produced synergistic beneficial effects leading to dramatic attenuation of renal tubulointerstitial fibrosis in obstructive nephropathy in mice. The combined treatment with human HGF gene and losartan, an angiotensin II (AngII) type I receptor blocker, preserved renal mass and gross morphology of the obstructed kidneys. Although HGF gene therapy alone inhibited the expression of α-smooth muscle actin (αSMA) by approximately 54% and 60% at day 7 and day 14 after surgery, respectively, its combination with losartan almost completely abolished αSMA induction in the obstructed kidneys. The combined therapy also synergistically inhibited the accumulation of interstitial matrix components, such as fibronectin and collagen I, and suppressed renal expression of transforming growth factor-β1 (TGF-β1) and its type I receptor. <i>In vitro</i> studies revealed that AngII by itself did not induce αSMA, but it drastically potentiated TGF-β1-initiated αSMA expression in tubular epithelial cells. Furthermore, HGF abrogated <i>de novo</i> αSMA expression induced by TGF-β1 plus AngII. These results suggest that many factors are implicated in the pathogenesis of renal interstitial fibrosis; therefore, a combined therapy aimed at simultaneously targeting multiple pathologic pathways may be necessary for halting the progression of chronic renal diseases. These findings may provide the basis for designing future therapeutic regimens for blocking progressive renal fibrosis in patients. E-mail: liuy@msx.upmc.edu" @default.
- W2137169969 created "2016-06-24" @default.
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- W2137169969 date "2002-10-01" @default.
- W2137169969 modified "2023-10-07" @default.
- W2137169969 title "Hepatocyte Growth Factor Gene Therapy and Angiotensin II Blockade Synergistically Attenuate Renal Interstitial Fibrosis in Mice" @default.
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- W2137169969 doi "https://doi.org/10.1097/01.asn.0000031827.16102.c1" @default.
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