Hepatocyte growth factor-induced amelioration in renal interstitial fibrosis is associated with reduced expression of alpha-smooth muscle actin and transforming growth factor-beta 1

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-beta 1) expression. The animals were randomized into 8 groups comprising 6 animals (n = 6) each: control (group I), PCI-neo (group H, 900 mu g), 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 mu g), high-dose PCI-neo-HGF group (group VII, 1380 mu g) and lotensin + high-dose PCI-neo-HGF group (group VIII, 0.6 mg/100 g/day for 5 weeks, 1380 mu g). The animals were sacrificed in the 5(th) week after 5/6 nephrectomy. The specimens of kidneys were used for pathological examination (hematoxylin-eosin staining), detection of alpha-SMA and TGF-beta 1 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-beta 1 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 alpha-SMA and TGF-beta 1 expressions.