Katsumoto Tamiko R, Violette Shelia M, Sheppard Dean
Department of Medicine, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA 94143, USA.
Int J Rheumatol. 2011;2011:208219. doi: 10.1155/2011/208219. Epub 2011 Oct 16.
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.
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。
