Hepatocyte growth factor prevents pulmonary ischemia-reperfusion injury in mice.
BACKGROUND
Ischemia-reperfusion (IR) injury after lung transplantation leads to significant morbidity and mortality in recipients, which remains the major obstacle in clinical lung transplantation. To reduce pulmonary graft dysfunction and improve prognosis after lung transplantation, prevention of IR-induced lung injury in the peri-operative period is required. In the present study, we investigated the effects of recombinant hepatocyte growth factor (HGF) on pulmonary IR injury using a murine model system.


METHODS
To assess the protective effect of HGF against lung injury, mice with pulmonary IR were divided into two groups and injected with 500 microg/kg of human recombinant HGF or the same dose of saline alone as a control.


RESULTS
After pulmonary IR injury, the lung injury score increased in a time-dependent manner up to 24 hours. A significant reduction of lung injury score was observed with the administration of exogenous HGF. Moreover, the ratio of apoptotic cells was significantly reduced in mice treated with HGF. Significantly increased expression of Bcl-xL was observed after IR in mice administered HGF as compared with saline-treated controls. In contrast, expression of Bax was reduced significantly in HGF-treated mice. Serum levels of endogenous murine HGF were increased significantly in HGF-treated mice.


CONCLUSIONS
Our findings indicate that administration of exogenous HGF ameliorates the pulmonary tissue injury induced by IR, which may provide an alternative for prevention of IR-induced lung injury in the peri-operative period in lung transplantation.
Makiuchi
Akiko
A
Department of Surgery (II), Shinshu University School of Medicine, Matsumoto, Japan.
Yamaura
Kazuhiro
K
Mizuno
Shinya
S
Matsumoto
Kunio
K
Nakamura
Toshikazu
T
Amano
Jun
J
Ito
Ken-ichi
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D011650:Pulmonary Alveoli / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D017228:Hepatocyte Growth Factor