Hepatocyte growth factor prevents chronic allograft dysfunction in liver-transplanted rats

Tashiro, Hirotaka; Fudaba, Yasuhiro; Itoh, Hisao; Mizunuma, Kazuyuki; Ohdan, Hideki; Itamoto, Toshiyuki; Asahara, Toshimasa

doi:10.1097/01.tp.0000083040.50727.ce

Cited by 23 publications

(19 citation statements)

References 27 publications

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“…In the context of liver transplantation, exogenous HGF administration to recipients of reduced-size liver graft enhances early restoration of liver volume, stimulates hepatic regeneration, and provides protection from rejection injury (1,(46)(47)(48). The results of the present study indicate that both ischemic preconditioning and NO donor treatments protect against hepatic I/R injury and improve hepatic regeneration in ROLT.…”

Section: Discussionsupporting

confidence: 54%

“…Numerous investigations have demonstrated that HGF promotes hepatic growth and regeneration (1,13,15,16,(46)(47)(48). In the context of liver transplantation, exogenous HGF administration to recipients of reduced-size liver graft enhances early restoration of liver volume, stimulates hepatic regeneration, and provides protection from rejection injury (1,(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

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Protection of Reduced-Size Liver for Transplantation

Franco-Gou¹,

Peralta²,

Massip-Salcedo

et al. 2004

American Journal of Transplantation

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The shortage of available organs for liver transplantation has motivated the development of new surgical techniques such as reduced-size liver transplantation. Ischemia-reperfusion (I/R) associated with liver transplantation impairs liver regeneration. Ischemic preconditioning is effective against I/R injury in clinical practice of liver tumour resections. The present study evaluated the effect of ischemic preconditioning on reduced-size liver for transplantation and attempted to identify the underlying protective mechanisms. Hepatic injury and regeneration (transaminases, proliferating cell nuclear antigen [PCNA] labeling index, and hepatocyte growth factor [HGF]) were assessed after reduced-size orthotopic liver transplantation (ROLT). Energy metabolism, oxidative stress, tumor necrosis factor-a (TNF) and interleukin-6 (IL-6) were examined as possible mechanisms involved in liver regeneration. Ischemic preconditioning reduced transaminase levels and increased HGF levels and the percentage of PCNApositive hepatocytes after ROLT. This was associated with a decrease in oxidative stress following ROLT, whereas energy metabolism and hepatic IL-6 and TNF release were unchanged. The benefits of ischemic preconditioning on hepatic injury and liver regeneration could be mediated, at least partially by nitric oxide. These results suggest a new potential application of ischemic preconditioning in reduced-size liver transplantation.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Protection of Reduced-Size Liver for Transplantation

Franco-Gou¹,

Peralta²,

Massip-Salcedo

et al. 2004

American Journal of Transplantation

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“…23,24 However, it still remained uncertain whether tolerance could be induced by HGF in each model. In our study, administration of HGF could induce tolerance in the recipient, which was an unexpected but favorable effect on cardiac allografts.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Acute and Chronic Rejection by Hepatocyte Growth Factor in a Murine Model of Cardiac Transplantation

et al. 2004

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Background— Although treatment with immunosuppressive agents has contributed to overcoming acute rejection and improving the midterm survival of transplanted hearts, cardiac allograft vasculopathy (CAV) has remained the main cause of primary graft failure. Recent approaches have shown that hepatocyte growth factor (HGF) exhibits cardiotrophic functions. We therefore addressed whether HGF would regulate acute and chronic rejection in cardiac transplantation. Methods and Results— We used a murine heterotopic cardiac transplantation model between fully incompatible strains and administered 500 μg · kg −1 · d −1 HGF during the initial 14 days after transplantation. The HGF-treated allografts showed significantly prolonged survival (42.3±4.1 days, P <0.001) compared with the controls (11.1±0.6 days), with tolerance induction in 47.4%. Histopathologically, the number of infiltrating cells was significantly decreased and myocardial necrosis was less prominent with a reduction of apoptosis in the allografts by HGF treatment during acute rejection. In the long-term surviving allografts, HGF significantly inhibited the development of CAV and interstitial fibrosis. With respect to intragraft cytokine mRNA expression, HGF treatment reduced the early expression of interferon-γ and enhanced the expression of transforming growth factor-β1 during the acute phase and of interleukin-10 continuously through the acute phase to the chronic phase. Conclusions— Our findings demonstrate that HGF can prolong the survival of allografts by its cardioprotective and immunomodulative potencies. Thus, HGF administration may constitute a new therapeutic approach to preventing cardiac graft failure that has not been overcome by conventional immunosuppressive agents.

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“…Several authors have demonstrated that HGF is crucial in promoting liver regeneration following partial hepatectomy and transplantation in animal models [63][64][65][66][67] . HGF administration to recipients of reduced-size liver grafts in rats illustrated early regeneration and provided hepatoprotection against rejection-related injuries [64,68,69] . These essential signals are regulated by HGF, via c-met, the gene on the HGF-receptor.…”

Section: Growth Factors and Growth-factor Signaling Systems In Liver mentioning

confidence: 99%

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

Gomez¹

2007

WJG

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Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemicreperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords "liver", "ischaemic reperfusion", "ischaemic preconditioning", "regeneration", "hepatectomy" and "transplantation". The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growthpromoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation.

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Hepatocyte growth factor prevents chronic allograft dysfunction in liver-transplanted rats

Abstract: The findings indicate that dHGF may prevent chronic liver-allograft dysfunction and thus may become a novel treatment for chronic liver-allograft dysfunction.

Cited by 23 publications

References 27 publications

Protection of Reduced-Size Liver for Transplantation

Protection of Reduced-Size Liver for Transplantation

Suppression of Acute and Chronic Rejection by Hepatocyte Growth Factor in a Murine Model of Cardiac Transplantation

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

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