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通过抑制αvβ6整合素阻断转化生长因子β:系统性硬化症间质性肺病的一种可能治疗方法。

Blocking TGFβ via Inhibition of the αvβ6 Integrin: A Possible Therapy for Systemic Sclerosis Interstitial Lung Disease.

作者信息

Katsumoto Tamiko R, Violette Shelia M, Sheppard Dean

机构信息

Department of Medicine, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA 94143, USA.

出版信息

Int J Rheumatol. 2011;2011:208219. doi: 10.1155/2011/208219. Epub 2011 Oct 16.


DOI:10.1155/2011/208219
PMID:22013449
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3195527/
Abstract

Interstitial lung disease (ILD) is a commonly encountered complication of systemic sclerosis (SSc) and accounts for a significant proportion of SSc-associated morbidity and mortality. Its pathogenesis remains poorly understood, and therapies that treat SSc ILD are suboptimal, at best. SSc ILD pathogenesis may share some common mechanisms with other fibrotic lung diseases, in which dysregulation of lung epithelium can contribute to pathologic fibrosis via recruitment or in situ generation and activation of fibroblasts. TGFβ, a master regulator of fibrosis, is tightly regulated in the lung by the integrin αvβ6, which is expressed at low levels on healthy alveolar epithelial cells but is highly induced in the setting of lung injury or fibrosis. Here we discuss the biology of αvβ6 and present this integrin as a potentially attractive target for inhibition in the setting of SSc ILD.

摘要

间质性肺疾病(ILD)是系统性硬化症(SSc)常见的并发症,在SSc相关的发病和死亡中占很大比例。其发病机制仍知之甚少,目前治疗SSc ILD的疗法充其量也只是次优的。SSc ILD的发病机制可能与其他纤维化性肺病有一些共同机制,在这些疾病中,肺上皮细胞的失调可通过募集或原位生成及激活成纤维细胞而导致病理性纤维化。转化生长因子β(TGFβ)是纤维化的主要调节因子,在肺中受整合素αvβ6的严格调控,整合素αvβ6在健康肺泡上皮细胞上低水平表达,但在肺损伤或纤维化情况下会高度诱导表达。在此,我们讨论αvβ6的生物学特性,并提出该整合素作为SSc ILD情况下潜在有吸引力的抑制靶点。

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Blocking TGFβ via Inhibition of the αvβ6 Integrin: A Possible Therapy for Systemic Sclerosis Interstitial Lung Disease.

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[6]
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[7]
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[9]
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[10]
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本文引用的文献

[1]
Epithelium-specific deletion of TGF-β receptor type II protects mice from bleomycin-induced pulmonary fibrosis.

J Clin Invest. 2010-12-6

[2]
The pathogenesis of systemic sclerosis.

Annu Rev Pathol. 2011

[3]
Clinical course and prediction of survival in idiopathic pulmonary fibrosis.

Am J Respir Crit Care Med. 2010-10-8

[4]
The polarization of immune cells in the tumour environment by TGFbeta.

Nat Rev Immunol. 2010-7-9

[5]
Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: clinical, radiologic, histopathologic, and treatment evidence.

Semin Arthritis Rheum. 2010-5-21

[6]
Epithelial cells promote fibroblast activation via IL-1alpha in systemic sclerosis.

J Invest Dermatol. 2010-5-6

[7]
Pathogenesis of pulmonary fibrosis in systemic sclerosis: lessons from interstitial lung disease.

Curr Rheumatol Rep. 2010-2

[8]
Does chronic microaspiration cause idiopathic pulmonary fibrosis?

Am J Med. 2010-4

[9]
Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis.

Am J Respir Crit Care Med. 2009-10-22

[10]
A TGFbeta-responsive gene signature is associated with a subset of diffuse scleroderma with increased disease severity.

J Invest Dermatol. 2009-10-8

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