Gene therapy for renal anemia in mice with polycystic kidney using an adenovirus vector encoding the human erythropoietin gene

被引:31
作者
Osada, S
Ebihara, I
Setoguchi, Y
Takahashi, H
Tomino, Y
Koide, H
机构
[1] Koto Hosp, Dept Med, Koto Ku, Tokyo 136, Japan
[2] Juntendo Univ, Sch Med, Dept Med, Div Nephrol, Tokyo 113, Japan
[3] Juntendo Univ, Sch Med, Dept Med, Div Resp Dis, Tokyo 113, Japan
[4] Fujita Hlth Univ, Inst Comprehens Med Sci, Lab Anim Ctr, Toyoake, Aichi, Japan
关键词
recombinant human erythropoietin; mesothelial cell; DBA/2FG-pcy mouse; gene therapy; end-stage renal disease; polycystic kidney disease;
D O I
10.1046/j.1523-1755.1999.00381.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background Recombinant human erythropoietin (rHuEPO) is primarily used for patients with anemia associated with endstage renal disease. We evaluated the efficacy of EPO gene therapy using adenovirus vector for chronic renal failure mice expressing severe renal anemia. Methods. Recombinant HuEPO gene transfer to mesothelial cells was performed in vitro and in vivo. Recombinant replication-deficient adenoviruses containing rHuEPO cDNA (AdCMVEPO), E. coli lacZ gene (AdCMVlacZ), or an nonexogenous gene (AdNull as control vector) driven by the cytomegalovirus promotor/enhancer were constructed. The oligosaccharides associated with the rHuEPO from AdCMVEPO-treated mesothelial cells were analyzed. For in vivo study, the DBA/2FG-pcy mouse, a model for human autosomal recessive polycystic kidney disease resulting in chronic renal failure with progressive anemia, was used. Results. The sialylated oligosaccharides associated with the rHuEPO produced in AdCMVEPO-treated mesothelial cells occupied 78 +/- 0.7% of the total oligosaccharide pool. A single intraperitoneal administration of AdCMVEPO induced rHuEPO synthesis in the peritoneal cells and a marked increase in erythrocyte production. The maximal increase in hematocrit (43 +/- 4%) was observed on day 28, and it remained elevated for 40 days. Conclusion. These results indicate that intraperitoneal administration of AdCMVEPO improves renal anemia in mice with chronic renal failure and that the mesothelial cell is an appropriate target cell for gene transfer.
引用
收藏
页码:1234 / 1240
页数:7
相关论文
共 28 条
  • [11] Insertion of the adenoviral E3 region into a recombinant viral vector prevents antiviral humoral and cellular immune responses and permits long-term gene expression
    Ilan, Y
    Droguett, G
    Chowdhury, NR
    Li, YA
    Sengupta, K
    Thummala, NR
    Davidson, A
    Chowdhury, JR
    Horwitz, MS
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) : 2587 - 2592
  • [12] PHYSICOCHEMICAL AND BIOLOGICAL CHARACTERIZATION OF ASIALOERYTHROPOIETIN - SUPPRESSIVE EFFECTS OF SIALIC-ACID IN THE EXPRESSION OF BIOLOGICAL-ACTIVITY OF HUMAN ERYTHROPOIETIN INVITRO
    IMAI, N
    HIGUCHI, M
    KAWAMURA, A
    TOMONOH, K
    OHEDA, M
    FUJIWARA, M
    SHIMONAKA, Y
    OCHI, N
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1990, 194 (02): : 457 - 462
  • [13] ANEMIA IN NEW CONGENITAL ADULT TYPE POLYCYSTIC KIDNEY MICE
    KOUMEGAWA, JI
    NAGANO, N
    ARAI, H
    WADA, M
    KUSAKA, M
    TAKAHASHI, H
    [J]. JOURNAL OF UROLOGY, 1991, 146 (06) : 1645 - 1649
  • [14] THE MOLECULAR MECHANISM OF ERYTHROPOIETIN ACTION
    KOURY, MJ
    BONDURANT, MC
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 210 (03): : 649 - 663
  • [15] KOURY ST, 1988, BLOOD, V71, P524
  • [16] SUSTAINED DELIVERY OF ERYTHROPOIETIN IN MICE BY GENETICALLY-MODIFIED SKIN FIBROBLASTS
    NAFFAKH, N
    HENRI, A
    VILLEVAL, JL
    ROUYERFESSARD, P
    MOULLIER, P
    BLUMENFELD, N
    DANOS, O
    VAINCHENKER, W
    HEARD, JM
    BEUZARD, Y
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (08) : 3194 - 3198
  • [17] NIELSEN OJ, 1987, BLOOD, V70, P1904
  • [18] NISSENSON AR, 1991, AM J KIDNEY DIS, V18, P1
  • [19] PAVLOVICKENTERA V, 1987, EXP HEMATOL, V15, P785
  • [20] SEGUCHI C, 1992, CLIN CHEM, V38, P199