Koh D W, Roby J D, Starcher B, Senior R M, Pierce R A
Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
Am J Respir Cell Mol Biol. 1996 Nov;15(5):611-23. doi: 10.1165/ajrcmb.15.5.8918368.
Elastic and collagen fibers confer recoil and tensile strength on the pulmonary vasculature, airways, alveolar walls, and pleura. These durable extracellular matrix components are primarily synthesized during lung development and growth, and are expressed at very low levels in healthy adult lung. However, reinitiation of elastin and collagen synthesis in diseases of adult lung, such as idiopathic pulmonary fibrosis, often leads to excessive or aberrant deposition of elastin and collagen which contribute to the pathophysiology of these diseases. We used an experimental model of postpneumonectomy lung growth to determine whether normal patterns of synthesis and deposition of these critical structural components can occur in the adult lung. Male Sprague-Dawley rats (250-300 grams) were subjected to left pneumonectomy and right lobectomy. The remaining lung tissue was harvested for analysis after 3, 7, or 14 days. Compensatory growth of the remaining right lung progressed throughout the time course. Total desmosine and hydroxyproline content increased in the postpneumonectomy lung, reflecting increased elastin and collagen accumulation, but both were normal in content per weight of lung tissue. Northern analysis demonstrated induction of tropoelastin and type I procollagen mRNA expression in lungs of pneumonectomy rats. In situ hybridization localized tropoelastin and type I procollagen mRNA expression to anatomical sites similar to those seen during lung development. These data indicate that the adult lung can reinitiate elastin and collagen production and deposit these extracellular matrix components in a normal pattern.
弹性纤维和胶原纤维赋予肺血管系统、气道、肺泡壁和胸膜弹性和抗张强度。这些耐用的细胞外基质成分主要在肺发育和生长过程中合成，在健康成年肺中表达水平极低。然而，在诸如特发性肺纤维化等成年肺疾病中，弹性蛋白和胶原合成的重新启动常常导致弹性蛋白和胶原过度或异常沉积，这促成了这些疾病的病理生理学过程。我们使用肺切除术后肺生长的实验模型来确定这些关键结构成分的正常合成和沉积模式是否能在成年肺中发生。雄性Sprague-Dawley大鼠（250 - 300克）接受左肺切除术和右肺叶切除术。在3、7或14天后收获剩余的肺组织进行分析。在整个时间进程中，剩余右肺的代偿性生长持续进行。肺切除术后肺中总锁链素和羟脯氨酸含量增加，反映出弹性蛋白和胶原积累增加，但每单位肺组织重量的含量均正常。Northern分析表明肺切除大鼠肺中前弹性蛋白和I型前胶原mRNA表达上调。原位杂交将前弹性蛋白和I型前胶原mRNA表达定位到与肺发育过程中所见相似的解剖部位。这些数据表明成年肺能够重新启动弹性蛋白和胶原的产生，并以正常模式沉积这些细胞外基质成分。
