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Article type: Research Article
Authors: Hiyoshi, Mineyoshi | Ohkubo, Tomoichi | Tsuji, Kimiyoshi | Hagihara, Masao | Nakasaki, Hisao | Mukai, Masaya | Makuuchi, Hiroyasu | Yamamura, Masaichi | Tsuda, Michio
Affiliations: Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193 Japan | Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193 Japan | Department of Surgical Medicine, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193 Japan
Note: [] Corresponding author: Michio Tsuda, Department of Molecular Life Science, Tokai University, School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193 Japan. Tel.: +81 463 93 1121, ext.2552; Fax: +81 463 96 4828; E-mail: mtsuda@is.icc.u-tokai.ac.jp
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.
Keywords: hepatocyte proliferation factor (HPF), DNA synthesis, purification, growth factor
Journal: BioFactors, vol. 16, no. 1-2, pp. 1-14, 2002
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