Hepatocyte Peroxisome Proliferator-Activated Receptor alpha Enhances Liver Regeneration after Partial Hepatectomy in Mice
Hepatocyte Peroxisome Proliferator-Activated Receptor alpha Enhances Liver Regeneration after Partial Hepatectomy in Mice
复制标题
肝细胞过氧化物酶体增殖物激活受体α增强小鼠部分肝切除术后的肝脏再生
DOI：
10.1016/j.ajpath.2018.10.009
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发表时间：
2019
影响因子：
6
通讯作者：
Qu Aijuan
中科院分区：
文献类型：
--
作者：
Xie Guomin;Yin Shi;Zhang Zhenzhen;Qi Dan;Wang Xia;Kim Donghwan;Yagai Tomoki;Brocker Chad N.;Wang Yan;Gonzalez Frank J.;Wang Hua;Qu Aijuan
过氧化物酶体增殖体激活受体α (PPARα)是参与脂质稳态控制的关键核受体。在啮齿动物中，PPARα也是一种有效的肝有丝分裂原。肝细胞特异性阻断PPARα抑制激动剂诱导的肝细胞增殖然而，关于PPARα在部分肝切除术（PHx）诱导的肝再生中的确切作用知之甚少。本实验以肝细胞特异性PPARα缺陷（PparaΔHep）小鼠为实验对象，研究了肝细胞PPARα在phx诱导的肝再生中的作用。PHx后肝脏PPARα蛋白水平和转录活性升高。与parafl/flmice相比，PparaΔHepmice在PHx后32小时的肝细胞增殖明显减少。同样，在PHx 32小时后，观察到ccnd1、pcnamrna和CYCD1的减少以及增殖的细胞核抗原蛋白inPparaΔHepmice。此外，PparaΔHepmice与pparafl /flmice相比，由于肝脏脂肪酸β-氧化受损，肝脏脂质积累增加，肝脏甘油三酯含量增加。这些结果表明，PPARα促进PHx后肝脏再生，至少部分是通过调节细胞周期和脂质代谢。
Peroxisome proliferator–activated receptor α (PPARα) is a key nuclear receptor involved in the control of lipid homeostasis. In rodents, PPARα is also a potent hepatic mitogen. Hepatocyte-specific disruption of PPARα inhibits agonist-induced hepatocyte proliferation; however, little is known about the exact role of PPARα in partial hepatectomy (PHx)–induced liver regeneration. Herein, using hepatocyte-specific PPARα-deficient (PparaΔHep) mice, the function of hepatocyte PPARα in PHx-induced liver regeneration was investigated. PPARα protein level and transcriptional activity were increased in the liver after PHx. Compared with thePparafl/flmice,PparaΔHepmice exhibited significantly reduced hepatocyte proliferation at 32 hours after PHx. Consistently, reducedCcnd1andPcnamRNA and CYCD1 and proliferating cell nuclear antigen protein were observed at 32 hours after PHx inPparaΔHepmice. Furthermore,PparaΔHepmice showed increased hepatic lipid accumulation and enhanced hepatic triglyceride contents because of impaired hepatic fatty acid β-oxidation when compared with that observed inPparafl/flmice. These results indicate that PPARα promotes liver regeneration after PHx, at least partially via regulating the cell cycle and lipid metabolism.