Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn
Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn
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DOI：
10.1002/hep.22126
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发表时间：
2008-03-01
期刊：
影响因子：
13.5
通讯作者：
Wu, Chu-Tse
中科院分区：
文献类型：
--
作者：
Cui, Chun-Ping;Zhang, Da-Jin;Wu, Chu-Tse
肝刺激物质（HSS）于1975年首次从断奶大鼠肝脏中分离出来，并在体外和体内发现了刺激肝脏DNA合成的作用。从那时起，哺乳动物和人类的HSS已经被研究用于治疗肝脏疾病的潜力。然而，由于HSS尚未完全纯化，其组成和结构的本质仍然是一个谜。采用加热法、乙醇沉淀法和离子交换色谱法从新生小牛肝脏中分离出具有特异性刺激活性的蛋白，并采用[H-3]胸苷脱氧核糖(TdR)/溴脱氧尿苷（BrdU）结合法和基于羧基荧光素二乙酸琥珀酰氨基酯（CFSE）的增殖试验测定其体外和体内生物活性。我们报道了从小牛肝HSS粗提取物中纯化一种新的30kda蛋白。该蛋白是富含亮氨酸的酸性核蛋白家族（LANP）的成员，被命名为肝生成素Cn （HPPCn）。对部分肝切除（PH）小鼠的研究表明，肝损伤后HPPCn信使RNA （mRNA）水平升高。此外，重组人蛋白（rhHPPCn）在体外和体内均可刺激肝脏DNA合成并激活参与肝细胞增殖的信号通路。结论：HPPCn是一种新型的肝脏生长因子，在肝脏再生中起重要作用。
Hepatic stimulating substance (HSS) was first isolated from weanling rat liver in 1975 and found to stimulate hepatic DNA synthesis both in vitro and in vivo. Since then, mammalian and human HSS have been investigated for their potential to treat hepatic diseases. However, the essential nature in composition and structure of HSS remain puzzling because HSS has not been completely purified. Heating, ethanol precipitation, and ion-exchange chromatographies had been carried out to isolate the protein with specific stimulating activity from newborn calf liver, and [H-3]thymidine deoxyribose (TdR)/bromodeoxyuridine (BrdU) incorporation and carboxyfluorescein diacetate succinimidyl ester (CFSE)-based proliferation assay to determine the bioactivity in vitro and in vivo. We report the purification of a novel 30-kDa protein from a crude extract of calf liver HSS. This protein is a member of the leucine-rich acidic nuclear protein family (LANP) and has been named hepatopoietin Cn (HPPCn). Studies of partially hepatectomized (PH) mice show that levels of HPPCn messenger RNA (mRNA) increase after liver injury. Furthermore, the recombinant human protein (rhHPPCn) was shown to stimulate hepatic DNA synthesis and activate signaling pathways involved in hepatocyte proliferation in vitro and in vivo. Conclusion: HPPCn is a novel hepatic growth factor that plays a role in liver regeneration.