Hepatocyte growth factor-induced amelioration in renal interstitial fibrosis is associated with reduced expression of alpha-smooth muscle actin and transforming growth factor-beta1.
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| Abstract |
Several studies have shown that hepatocyte growth factor (HGF) ameliorates renal interstitial fibrosis, but the mechanism is not fully clear. This study was designed to examine whether HGF can relieve renal interstitial injury in 5/6 nephrectomized rats, and to confirm whether this function was associated with decrease in alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-betal (TGF-beta1) expression. The animals were randomized into 8 groups comprising 6 animals (n = 6) each: control (group I), PCI-neo (group II, 900 microg), sham-operation (group III, not nephrectomy), model or 5/6 nephrectomy group (group IV), lotensin group (an angiotensin converting enzyme inhibitor, group V, 0.6 mg/100 g/day for 5 weeks), low-dose PCI-neo-HGF group (group VI, 690 microg), high-dose PCI-neo-HGF group (group VII, 1380 microg) and lotensin + high-dose PCI-neo-HGF group (group VIII, 0.6 mg/100 g/day for 5 weeks, 1380 microg). The animals were sacrificed in the 5th week after 5/6 nephrectomy. The specimens of kidneys were used for pathological examination (hematoxylin-eosin staining), detection of alpha-SMA and TGF-beta1 mRNA (Reverse transcriptase-polymerase chain reaction) and protein (Western blot and immunohistochemistry) expression. The results showed that in 5/6 nephrectomized rats blood urea nitrogen (BUN), serum creatinine (CRE) and 24 h urinary albumin excretion (UAE) were increased, renal interstitium was injured seriously and alpha-SMA, TGF-beta1 mRNA and protein expression were elevated compared with those of control. The above changes were ameliorated and alpha-SMA and TGF-beta 1 expression was reduced by both PCI-neo-HGF and lotensin. The lotensin + high-dose PCI-neo-HGF group rats exhibited the most significant therapeutic effect both in decreasing the BUN, CRE and 24 h UAE and in relieving renal interstitial injury. In conclusion, the study demonstrated that HGF can relieve renal interstitial injury and this protection was associated with down-regulation of a-SMA and TGF-beta 1 expressions.
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| Authors | Hong-yue Wang, Yan-jun Wang, Ming-ji Cui, Chun-mei Gu, Li-zhi Yang, Ying Zhao, Yan Chen, Dan Zhao, Tian-shu Li, Bao-rong Chi |
| Journal | Indian journal of biochemistry & biophysics (Indian J Biochem Biophys) Vol. 48 Issue 5 Pg. 308-15 (Oct 2011) ISSN: 0301-1208 [Print] India |
| PMID | 22165288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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