title: Hepatocyte proliferation factors from neonatal pig liver: purification and characterization.
abstract: Two factors were found in the condition medium of neonatal pig liver fragments, which were capable of stimulating DNA synthesis in primary hepatocytes. They were named hepatocyte proliferation factor (HPF)-1 and HPF-2 and purified 1,025- and 2,580-fold, respectively. Both HPF-1 and HPF-2 seem to be anionic at pH 8.0 judged from the elution pattern of DEAE (DE52) column chromatography. HPF-1 was recovered as a non-adsorbed fraction in blue Sepharose and heparin Sepharose columns, and had a molecular weight of 26-31 kDa as estimated by gel filtration in high salt condition. Purified HPF-1 stimulated DNA synthesis of primary rat hepatocytes, but suppressed that of HepG2 cells. HPF-2 strongly bound to blue Sepharose and heparin Sepharose columns, and had a molecular weight of 71-90 kDa as estimated by SDS-PAGE under non-reduced condition. Purified HPF-2 stimulated DNA synthesis of primary rat hepatocytes dose dependently but did not suppress that of HepG2 cells. From further biological and chemical characteristics studied in this paper, HPF-1 and HPF-2 may be novel stimulating proteins for hepatocyte proliferation, although the possibility that they are already known growth factors can not be excluded without complete purification and its cloning.
authors.affiliation: Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193 Japan.
authors.forename: Mineyoshi
authors.initials: M
authors.lastname: Hiyoshi
authors.forename: Tomoichi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Tsuji
authors.forename: Masao
authors.initials: M
authors.lastname: Hagihara
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakasaki
authors.forename: Masaya
authors.initials: M
authors.lastname: Mukai
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Makuuchi
authors.forename: Masaichi
authors.initials: M
authors.lastname: Yamamura
authors.forename: Michio
authors.initials: M
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D006528:Carcinoma, Hepatocellular; D002478:Cells, Cultured; D002850:Chromatography, Gel; D004247:DNA / Q000096:biosynthesis; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D006133:Growth Substances / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000737:chemistry*; D008113:Liver Neoplasms; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D014407:Tumor Cells, Cultured
chemical_list: D006133:Growth Substances; D004247:DNA