Premium
Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn
Author(s) -
Cui ChunPing,
Zhang DaJin,
Shi BingXing,
Du ShaoJun,
Wu DanLi,
Wei Ping,
Zhong GenShen,
Guo ZiKuan,
Liu Yang,
Wang LiSheng,
Wu ChuTse
Publication year - 2008
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22126
Subject(s) - in vivo , liver regeneration , in vitro , bromodeoxyuridine , dna synthesis , hepatocyte , biology , microbiology and biotechnology , biochemistry , hepatic stellate cell , messenger rna , protein biosynthesis , growth factor , chemistry , cell growth , regeneration (biology) , endocrinology , gene , receptor
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 [ 3 H]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. (H EPATOLOGY 2008;47:986–995.)