Hepatocyte growth factor-induced amelioration in chronic renal failure is associated with reduced expression of α-smooth muscle actin.
This study aimed to examine whether hepatocyte growth factor (HGF) can improve renal function in 5/6 nephrectomized rats and investigate whether this function is associated with a decrease in α-smooth muscle actin (α-SMA) expression in rat glomerulus mesangial cells and renal interstitium. Rats were randomly divided into the following groups: control, PCI-neo, sham-operation, 5/6 nephrectomy, and low-dose and high-dose PCI-neo-HGF. Rats were killed in the ninth week after 5/6 nephrectomy, and the kidney specimens were subjected to pathological examination by Hematoxylin-Eosin staining and detection of α-SMA expression by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. The results showed that blood urea nitrogen and serum creatinine levels were increased, renal interstitium was injured, and α-SMA expression was elevated in 5/6 nephrectomized rats compared with that in control. The above changes were ameliorated in the rats injected with PCI-neo-HGF vector. At the molecular level we found that PCI-neo-HGF repressed α-SMA expression in mesangial cells stimulated by lipopolysaccharide. In conclusion, our data suggest that HGF can relieve chronic renal failure, and this protection is associated with the down-regulation of α-SMA expression in mesangial cells and renal interstitium.
Department of Nephrology, First Hospital of Jilin University, Changchun, China.
Hong-yue
HY
Wang
Li-zhi
LZ
Yang
Ming-ji
MJ
Cui
Chun-mei
CM
Gu
Ying
Y
Zhao
Yan
Y
Chen
Dan
D
Zhao
Tian-shu
TS
Li
Baorong
B
Chi
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism*; D009392:Nephrectomy; D011507:Proteinuria / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors
D000199:Actins; D024042:Collagen Type I; D017228:Hepatocyte Growth Factor; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat