Remote delivery and expression of soluble type II TGF-β receptor in muscle prevents hepatic fibrosis in rats

被引：10

作者：

Nakamuta, M ^{[1
]}

Morizono, S ^{[1
]}

Tsuruta, S ^{[1
]}

Kohjima, M ^{[1
]}

Kotoh, K ^{[1
]}

Enjoji, M ^{[1
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 8128582, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2005年 / 16卷 / 01期

关键词：

soluble TGF-beta receptor; type I collagen; Th1/Th2; cytokines; biofactory; intramuscular injection;

D O I：

暂无

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Transforming growth factor-beta (TGF-beta) has been implicated in the process of hepatic fibrosis, and stimulates production of extracellular matrix in hepatic stellate cells, which play a major role in the process. It has been recently reported that blockage of TGF-beta signaling prevents hepatic fibrosis. We evaluated a strategy for anti-TGF-beta gene therapy for hepatic fibrosis by transfecting plasmids expressing an entire extracellular domain of human TGF-beta type II [soluble type II TGF-beta receptor (sTGF-beta IIR)] into skeletal muscle in a rat experimental model of dimethylnitrosamine- (DMN-) induced fibrosis. sTGF-beta IIR treatment decreased significantly the occurrence of DMN-induced hepatic fibrosis, evaluated by computed image analysis and by measurement of hydroxyproline content of the liver, and reduced the expression of collagen and a-smooth muscle actin. The treatment also caused a significant decrease in hepatic levels of interleukin- (IL-) 12 (Th1 cytokine) and an increase in those of IL-10 (Th2 cytokine), indicating a change in the Th1/Th2 cytokine balance in the liver. In conclusion, blockade of TGF-beta after intramuscular transfer of the soluble type II TGF-beta receptor gene suppressed hepatic fibrosis, suggesting that this strategy may be useful for gene therapy of hepatic fibrosis.

引用

页码：59 / 64

页数：6

共 45 条

[41] DIRECT GENE-TRANSFER INTO MOUSE MUSCLE INVIVO [J].

WOLFF, JA ;

MALONE, RW ;

WILLIAMS, P ;

CHONG, W ;

ACSADI, G ;

JANI, A ;

FELGNER, PL .

SCIENCE, 1990, 247 (4949) :1465-1468

[42] TGF-BETA SIGNALS THROUGH A HETEROMERIC PROTEIN-KINASE RECEPTOR COMPLEX [J].

WRANA, JL ;

ATTISANO, L ;

CARCAMO, J ;

ZENTELLA, A ;

DOODY, J ;

LAIHO, M ;

WANG, XF ;

MASSAGUE, J .

CELL, 1992, 71 (06) :1003-1014

[43] Lifetime exposure to a soluble TGF-β antagonist protects mice against metastasis without adverse side effects [J].

Yang, YA ;

Dukhanina, O ;

Tang, BW ;

Mamura, M ;

Letterio, JJ ;

MacGregor, J ;

Patel, SC ;

Khozin, S ;

Liu, ZY ;

Green, J ;

Anver, MR ;

Merlino, G ;

Wakefield, LM .

JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (12) :1607-1615

[44] Dose-dependent inhibition of hepatic fibrosis in mice by a TGF-β soluble receptor:: Implications for antifibrotic therapy [J].

Yata, Y ;

Gotwals, P ;

Koteliansky, V ;

Rockey, DC .

HEPATOLOGY, 2002, 35 (05) :1022-1030

[45] Blockade of TGF-β action ameliorates renal dysfunction and histologic progression in anti-GBM nephritis [J].

Zhou, AH ;

Ueno, H ;

Shimomura, M ;

Tanaka, R ;

Shirakawa, T ;

Nakamura, H ;

Matsuo, M ;

Iijima, K .

KIDNEY INTERNATIONAL, 2003, 64 (01) :92-101

← 1 2 3 4 5 →