PPARα is down-regulated following liver transplantation in mice.
PPARα is down-regulated following liver transplantation in mice.
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小鼠肝移植后，PPARα下调。
DOI：
10.1016/j.jhep.2011.08.021
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发表时间：
2012-03
影响因子：
25.7
通讯作者：
Aoyama T
中科院分区：
文献类型：
--
作者：
Nakagawa K;Tanaka N;Morita M;Sugioka A;Miyagawa S;Gonzalez FJ;Aoyama T
移植物功能障碍是肝移植术后的主要并发症之一，但其确切机制尚不清楚。由于脂肪变性肝移植物易发生移植后功能障碍，而过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）α在维持肝脏脂质稳态中起着重要作用，因此我们研究了过氧化物酶体增殖物激活受体α在肝移植中的作用。从Sv/129野生型（Ppara+/+）小鼠和PPARα-null（Ppara−/−）小鼠中收获肝脏，并原位移植到同基因Ppara+/+小鼠中。与Ppara+/+肝移植相比，Ppara−/−肝移植的肝细胞损伤意外地较轻。这可能是由于Ppara−/−肝脏中的脂质过氧化物减少，如脂肪酸氧化（FAO）酶（活性氧的主要来源）水平较低所揭示的。移植后肝脏PPARα及其靶基因，如FAO酶和丙酮酸脱氢酶激酶4，表达明显下调，这与肝脏肿瘤坏死因子-α表达和核因子-κB活性增加有关。通过氯贝丁酯治疗抑制移植后PPARα下调显著增强了氧化应激和肝细胞损伤。PPARα表达下调可能是肝移植后机体对代谢改变的一种适应性反应。这些结果为了解移植后早期事件的发病机制提供了新的信息。
Graft dysfunction is one of the major complications after liver transplantation, but its precise mechanism remains unclear. Since steatotic liver grafts are susceptible to post-transplant dysfunction, and peroxisome proliferator-activated receptor (PPAR) α plays an important role in the maintenance of hepatic lipid homeostasis, we examined the role of PPARα in liver transplantation. Livers were harvested from Sv/129 wild-type (Ppara+/+) mice and PPARα-null (Ppara−/−) mice and transplanted orthotopically into syngeneic Ppara+/+ mice. Hepatocellular damage was unexpectedly milder in transplanted Ppara−/− livers compared with Ppara+/+ ones. This was likely due to decreased lipid peroxides in the Ppara−/− livers, as revealed by the lower levels of fatty acid oxidation (FAO) enzymes, which are major sources of reactive oxygen species. Hepatic PPARα and its target genes, such as FAO enzymes and pyruvate dehydrogenase kinase 4, were strongly down-regulated after transplantation, which was associated with increases in hepatic tumor necrosis factor-α expression and nuclear factor-κB activity. Inhibiting post-transplant PPARα down-regulation by clofibrate treatment markedly augmented oxidative stress and hepatocellular injury. Down-regulation of PPARα seemed to be an adaptive response to metabolic alterations following liver transplantation. These results provide novel information to the understanding of the pathogenesis of early post-transplant events.
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影响因子：
3.6
作者：
Nakajima, Takero;Tanaka, Naoki;Aoyama, Toshifumi
通讯作者：
Aoyama, Toshifumi
DOI：
10.1111/j.1600-6143.2009.02859.x
发表时间：
2010-01
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Morita M;Fujino M;Jiang G;Kitazawa Y;Xie L;Azuma M;Yagita H;Nagao S;Sugioka A;Kurosawa Y;Takahara S;Fung J;Qian S;Lu L;Li XK
通讯作者：
Li XK
影响因子：
6.2
作者：
Fu, FM;Thai, NL;Qian, SG
通讯作者：
Qian, SG
影响因子：
4.6
作者：
Jiang, Xiaofeng;Morita, Miwa;Seino, Ken-ihiro
通讯作者：
Seino, Ken-ihiro
影响因子：
8.8
作者：
Berg, C. L.;Steffick, D. E.;Mazariegos, G. V.
通讯作者：
Mazariegos, G. V.