Progressive pulmonary fibrosis is mediated by TGF-β isoform 1 but not TGF-β3

被引：142

作者：

Ask, Kjetil ^{[2
]}

Bonniaud, Philippe ^{[2
,3
]}

Maass, Katja ^{[4
]}

Eickelberg, Oliver ^{[4
]}

Margetts, Peter J. ^{[2
]}

Warburton, David ^{[5
]}

Groffen, John ^{[5
]}

Gauldie, Jack ^{[2
]}

Kolb, Martin ^{[1
,2
]}

机构：

[1] McMaster Univ, Firestone Inst Resp Hlth, Dept Med, Hamilton, ON, Canada

[2] McMaster Univ, Ctr Gene Therapeut, Dept Pathol & Mol Med, Hamilton, ON, Canada

[3] Univ Bourgogne, CHU Bocage, Serv Pneumol & Reanimat Resp, Dijon, France

[4] Univ Giessen, Lung Ctr, Dept Med 2, Giessen, Germany

[5] Univ So Calif, Childrens Hosp Los Angeles, Saban Res Inst, Dev Biol Program, Los Angeles, CA 90089 USA

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2008年 / 40卷 / 03期

关键词：

growth factors; transforming growth factor beta; wound healing; lung fibrosis; extracellular matrix;

D O I：

10.1016/j.biocel.2007.08.016

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：

Tissue repair is a well-orchestrated biological process involving numerous soluble mediators, and an imbalance between these factors may result in impaired repair and fibrosis. Transforming growth factor (TGF)-beta is a key profibrotic element in this process and it is thought that its three isoforms act in a similar way. Here, we report that TGF-beta 3 administered to rat lungs using transient overexpression initiates profibrotic effects similar to those elicited by TGF-beta 1, but causes less severe and progressive changes. The data suggest that TGF-beta 3 does not lead to inhibition of matrix degradation in the same way as TGF-beta 1, resulting in non-fibrotic tissue repair. Further, TGF-beta 3 is able to downregulate TGF-beta 1-induced gene expression, suggesting a regulatory role of TGF-beta 3. TGF-beta 3 overexpression results in an upregulation of Smad proteins similar to TGF-beta 1, but is less efficient in inducing the ALK 5 and TGF-beta type II receptor (T beta RII). We provide evidence that this difference may contribute to the progressive nature of TGF beta 1-induced fibrotic response, in contrast to the limited fibrosis observed following TGF-beta 3 overexpression. TGF-beta 3 is important in "normal wound healing", but is outbalanced by TGF-beta I in "fibrotic wound healing" in the lung. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：484 / 495

页数：12

共 38 条

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