title: Pathological changes, TGF-β1 expression, and the effects of hepatocyte growth factor in 5/6 nephrectomized rats.
abstract: Several studies have shown that hepatocyte growth factor (HGF) ameliorates chronic renal failure, but its mechanism of action is unclear. This study was designed to test the delivery of HGF in the PCI-neo vector, using the 5/6 nephrectomized rat as a model for chronic renal failure, and to confirm that this protective function is associated with decreased protein expression of transforming growth factor-beta1 (TGF-β1). Rats were randomly divided into the following groups: Control (untreated), PCI-neo (vector control), 5/6 nephrectomy, and PCI-neo-HGF. Rats were sacrificed at both the fifth and ninth week after 5/6 nephrectomy. Kidney specimens were used for pathological examination (hematoxylin-eosin staining), and detection of TGF-β1 protein (Western blot and immunohistochemistry) expression. Blood urea nitrogen, serum creatinine, and 24-h urinary protein excretion (UPE) were increased, renal interstitium was seriously injured, and TGF-β1 protein expression was elevated in 5/6 nephrectomized rats compared to control rats at either time point. Red blood cell and hemoglobin levels decreased in the ninth week after 5/6 nephrectomy. PCI-neo-HGF expression ameliorated the aforementioned changes and decreased TGF-β1 expression, not only in the fifth week, but also in the ninth week after surgery. The process of renal injury in the 5/6 nephrectomized rat was consistent with that of chronic renal failure. The increase in TGF-β1 expression was maintained after 5/6 nephrectomy. HGF relieved chronic renal failure, this protection was associated with down-regulation of TGF-β1 protein expression, and the protective effects were long-term and stable after 5/6 nephrectomy.
authors.affiliation: Department of Nephrology, First Hospital of Jilin University , Changchun , China .
authors.forename: Hong-Yue
authors.initials: HY
authors.lastname: Wang
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Yang
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Gu
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Tian-Shu
authors.initials: TS
authors.lastname: Li
authors.forename: Ming-Ji
authors.initials: MJ
authors.lastname: Cui
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D015536:Down-Regulation; D004906:Erythrocyte Count; D006454:Hemoglobins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009392:Nephrectomy; D010957:Plasmids; D011507:Proteinuria; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D006454:Hemoglobins; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D003404:Creatinine