Isolation and functional identification of a novel human hepatic growth factor: hepatopoietin Cn.
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.


CONCLUSIONS
HPPCn is a novel hepatic growth factor that plays a role in liver regeneration.
Cui
Chun-Ping
CP
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, People's Republic of China.
Zhang
Da-Jin
DJ
Shi
Bing-Xing
BX
Du
Shao-Jun
SJ
Wu
Dan-Li
DL
Wei
Ping
P
Zhong
Gen-Shen
GS
Guo
Zi-Kuan
ZK
Liu
Yang
Y
Wang
Li-Sheng
LS
Wu
Chu-Tse
CT
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor