Endocrine expression of the active form of TGF-β1 in the TGF-β1 null mice fails to ameliorate lethal phenotype

被引：17

作者：

Longenecker, G

Thyagarajan, T

Nagineni, CN

Flanders, KC

Factor, V

Miller, G

Ward, JM

Nalca, A

Rangnekar, VM

Thorgeirsson, S

Kulkarni, AB

机构：

[1] Natl Inst Dent & Craniofacial Res, Funct Genom Unit & Gene Targeting Facil, NIH, Bethesda, MD 20892 USA

[2] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA

[3] NIH, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA

[4] Natl Canc Inst, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA

[5] NIH, Vet Resources Program, Off Director, Bethesda, MD 20892 USA

[6] Natl Canc Inst, Vet & Tumor Pathol Sect, Off Lab Sci, NIH, Ft Detrick, MD 21702 USA

[7] Univ Kentucky, Dept Radiat Med, Lexington, KY 40536 USA

来源：

CYTOKINE | 2002年 / 18卷 / 01期

基金：

美国国家卫生研究院;

关键词：

autoimmunity; cytokine therapy; glomerulonephritis; inflammation; TGF-beta; 1;

D O I：

10.1006/cyto.2002.1025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

TGF-beta1 null mice die by 3 to 4 weeks of age due to a severe autoimmune-mediated multifocal inflammation resulting in multi-organ failure. To assess the therapeutic potential of circulating levels of active TGF-beta1, we generated mice with endocrine expression of active TGF-beta1 on a TGF-beta1 null background (TGF-beta1 ((-/-/TG))) by crossing TGF-beta1((+/-)) mice with transgenic mice (TG) that express recombinant TGF-beta1 specifically in the liver and secrete it in the blood. The TGF-beta1 ((-/-/TG)) mice exhibit a survival profile similar to the TGF-beta1 ((-/-)) mice indicating a failure to rescue the lethal phenotype. However, serum TGF-beta1 levels in the TGF-beta1 ((-/-/TG)) mice were restored to near normal levels with expression in all the tissues, notably in the kidney and spleen. Histopathology showed reduced inflammation in the target tissues, especially in the heart. Interestingly, unlike TGF-beta1 ((-/-)) mice, the TGF-beta1 ((-/-/TG)) mice have glomerulonephritis in their kidneys similar to the TG mice. Thus, the phenotype of TGF-beta1 ((-/-/TG)) animal model indicates the potential role of circulating active-TGF-beta1 in reducing inflammation, but its failure to rescue lethality in TGF-beta1 null mice indicates a critical autocrine role of TGF-beta1. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：43 / 50

页数：8

共 56 条

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