title: Hepatocyte growth factor-induced amelioration in renal interstitial fibrosis is associated with reduced expression of alpha-smooth muscle actin and transforming growth factor-beta1.
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.
authors.affiliation: Department of Nephrology, First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Hong-yue
authors.initials: HY
authors.lastname: Wang
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Wang
authors.forename: Ming-ji
authors.initials: MJ
authors.lastname: Cui
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Gu
authors.forename: Li-zhi
authors.initials: LZ
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Tian-shu
authors.initials: TS
authors.lastname: Li
authors.forename: Bao-rong
authors.initials: BR
authors.lastname: Chi
mesh_terms: D000199:Actins / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000199:Actins; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor