Radiation-Induced Liver Fibrosis Is Mitigated by Gene Therapy Inhibiting Transforming Growth Factor-{beta} Signaling in the Rat

Journal Article · Wed Dec 01 00:00:00 EST 2010 · International Journal of Radiation Oncology, Biology and Physics

OSTI ID:21499704

Shisuo, Du; Ming, Qiang ^[1]; Jian, Zhou ^[2]; Yunshan, Tan ^[3]; Zhengyu, Zhang ^[1]; Haiying, Zeng ^[3]; Zhongshan, Liu ^[1]

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1. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)
2. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)
3. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)

Purpose: We determined whether anti-transforming growth factor-{beta} (TGF-{beta}) intervention could halt the progression of established radiation-induced liver fibrosis (RILF). Methods and Materials: A replication-defective adenoviral vector expressing the extracellular portion of human T{beta}RII and the Fc portion of immunoglobulin G fusion protein (AdT{beta}RIIFc) was produced. The entire rat liver was exposed to 30 Gy irradiation to generate a RILF model (RILFM). Then, RILFM animals were treated with AdT{beta}RIIFc (1 x 10{sup 11} plaque-forming units [PFU] of T{beta}RII), control virus (1 x 10{sup 11} PFU of AdGFP), or saline. Delayed radiation liver injury was assessed by histology and immunohistochemistry. Chronic oxidative stress damage, hepatic stellate cell activation, and hepatocyte regeneration were also analyzed. Results: In rats infected with AdT{beta}RIIFc, fibrosis was significantly improved compared with rats treated with AdGFP or saline, as assessed by histology, hydroxyproline content, and serum level of hyaluronic acid. Compared with AdGFP rats, AdT{beta}RIIFc-treated rats exhibited decreased oxidative stress damage and hepatic stellate cell activation and preserved liver function. Conclusions: Our results demonstrate that TGF-{beta} plays a critical role in the progression of liver fibrosis and suggest that anti-TGF-{beta} intervention is feasible and ameliorates established liver fibrosis. In addition, chronic oxidative stress may be involved in the progression of RILF.

• OSTI ID: 21499704
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 78, Issue 5; Other Information: DOI: 10.1016/j.ijrobp.2010.06.046; PII: S0360-3016(10)00898-9; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
FIBROSIS
GENE THERAPY
GROWTH FACTORS
LIVER
RADIATION INJURIES
RATS
STRESSES
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
DIGESTIVE SYSTEM
DISEASES
GLANDS
INJURIES
MAMMALS
MEDICINE
MITOGENS
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PROTEINS
RADIATION EFFECTS
RODENTS
THERAPY
VERTEBRATES