Delayed liver regeneration after partial hepatectomy in adipose differentiation related protein-null mice.
Delayed liver regeneration after partial hepatectomy in adipose differentiation related protein-null mice.
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DOI：
10.1016/j.jhep.2013.07.025
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发表时间：
2013-12
影响因子：
25.7
通讯作者：
Chan, Lawrence
中科院分区：
文献类型：
--
作者：
Kohjima, Motoyuki;Tsai, Tsung-Huang;Tackett, Bryan C.;Thevananther, Sundararajah;Li, Lan;Chang, Benny Hung-Junn;Chan, Lawrence
成年肝细胞经历细胞周期进展和增殖以响应部分肝切除术（PH）。在高峰增殖期之前肝细胞内的瞬时脂质积聚是再生肝脏的特征。然而，负责再生肝脏中脂质积累的分子介质和机制还不清楚。脂肪分化相关蛋白（ADRP; Plin 2）调节肝脏甘油三酯储存，Plin 2缺陷（Plin 2 −/−）小鼠肝脏中甘油三酯（TG）含量显著降低。我们试图确定PLIN 2在响应PH和毒性肝损伤的肝再生中的功能意义，并检查Plin 2表达的缺失是否调节肝细胞增殖和肝再生。我们对野生型（WT）和Plin 2 −/−小鼠进行70%PH或急性四氯化碳（CCL 4）治疗，并检查了治疗动物的肝脏脂质含量，脂质代谢相关基因的表达谱，细胞增殖速率和肝脏再生动力学。在对PH的反应中，Plin 2 −/−小鼠表现出肝脏甘油三酯积累减少和细胞周期进展延迟，这与肝脏再生受损有关。Plin 2 −/−和野生型小鼠之间的脂肪酸（FA）合成和脂质转移基因表达谱相当，而Plin 2 −/−小鼠的VLDL分泌率较高。Plin 2 −/−小鼠中β-氧化下调和胞质FA水平降低可能导致这些动物肝再生能力减弱。在平行实验中，我们还观察到Plin 2 −/−小鼠对CCl 4介导的急性毒性肝损伤的肝脏脂质蓄积和增殖反应减弱。我们得出结论，PLIN 2介导的脂质积累和利用的肝脏是重要的有效的肝再生响应PH和中毒性肝损伤。
Adult hepatocytes undergo cell cycle progression and proliferation in response to partial hepatectomy (PH). Transient lipid accumulation within hepatocytes preceding the peak proliferative phase is a characteristic feature of regenerating livers. However, the molecular mediators and mechanisms responsible for lipid accumulation in regenerating livers are not well understood. Adipose differentiation related protein (ADRP; Plin2) regulates hepatic triglyceride storage and Plin2-deficient (Plin2−/−) mice have significantly reduced triglyceride (TG) content in the liver. We sought to determine the functional significance of PLIN2 in liver regeneration in response to PH and toxic liver injury and examined whether absence of Plin2 expression modulates hepatocyte proliferation and liver regeneration. We subjected wild-type (WT) and Plin2−/− mice to 70% PH or acute carbon tetrachloride (CCL4) treatment and examined the hepatic lipid content, the expression profile of lipid metabolism-related genes, the rate of cellular proliferation and the dynamics of liver regeneration in the treated animals. In response to PH, Plin2−/− mice showed decreased hepatic triglyceride accumulation and delayed cell cycle progression, which was associated with impaired liver regeneration. Fatty acid (FA) synthesis and lipid transfer gene expression profile were comparable between Plin2−/− and wild-type mice, while VLDL secretion rate was higher in the Plin2−/− mice. Downregulated β-oxidation and reduced cytosolic FA level in Plin2−/− mice may have contributed to the attenuation of the liver regeneration capacity in these animals. In parallel experiments, we also observed attenuated hepatic lipid accumulation and proliferation in response to CCl4-mediated acute toxic liver injury in Plin2−/− mice. We conclude that PLIN2-mediated lipid accumulation and utilization by the liver is important for efficient liver regeneration in response to PH and toxic liver injury.
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DOI：
10.1016/0005-2760(69)90007-1
发表时间：
1969-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
INFANTE, R;ALCINDOR, G;CAROLI, J
通讯作者：
CAROLI, J
影响因子：
6.5
作者：
Kimmel AR;Brasaemle DL;McAndrews-Hill M;Sztalryd C;Londos C
通讯作者：
Londos C
影响因子：
6.5
作者：
Chang, Benny Hung-Junn;Li, Lan;Chan, Lawrence
通讯作者：
Chan, Lawrence
影响因子：
1.9
作者：
Greene, AK;Puder, M
通讯作者：
Puder, M
影响因子：
13.5
作者：
DeAngelis, RA;Markiewski, MM;Lambris, JD
通讯作者：
Lambris, JD