Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice |
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Authors: | Kanbe Takamasa Murai Rie Mukoyama Tomoyuki Murawaki Yoshiyuki Hashiguchi Ko-ichi Yoshida Yoko Tsuchiya Hiroyuki Kurimasa Akihiro Harada Ken-ichi Yashima Kazuo Nishimuki Eiji Shabana Noriko Kishimoto Yukihiro Kojyo Haruhiko Miura Kunihiko Murawaki Yoshikazu Kawasaki Hironaka Shiota Goshi |
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Affiliation: | Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan. |
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Abstract: | Ulcerative colitis (UC) is progressive and relapsing disease. To explore the therapeutic effects of naked gene therapy of hepatocyte growth factor (HGF) on UC, the SRalpha promoter driving HGF gene was intrarectally administered to the mice in which colitis was induced by dextran sulfate sodium (DSS). Expression of the transgene was seen in surface epithelium, lamina propria, and muscularis mucosae. The HGF-treated mice showed reduced colonic mucosal damage and increased body weights, compared with control mice (P < 0.01 and P < 0.05, respectively). The HGF-treated mice displayed increased number of PCNA-positive cells and decreased number of apoptotic cells than in control mice (P < 0.01, each). Phosphorylated AKT was dramatically increased after HGF gene administration, however, phosphorylated ERK1/2 was not altered. Microarray analysis revealed that HGF induced expression of proliferation- and apoptosis-associated genes. These data suggest that naked HGF gene delivery causes therapeutic effects through regulation of many downstream genes. |
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Keywords: | Hepatocyte growth factor Naked DNA Rectal administration Gene therapy Ulcerative colitis |
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