Sugahara K, Rubin J S, Mason R J, Aronsen E L, Shannon J M
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Am J Physiol. 1995 Sep;269(3 Pt 1):L344-50. doi: 10.1152/ajplung.1995.269.3.L344.
The production of pulmonary surfactant, a complex of phospholipids and lung-specific surfactant proteins, is a primary function of alveolar type II cells. Although previous studies have demonstrated a role for cell-extracellular matrix interactions and normal cell shape in the maintenance of differentiated function in primary cultures of adult rat type II cells, a positive role for growth factors in surfactant protein gene expression in isolated normal adult type II cells has not been reported. In the present study, we have examined the effects of a panel of hormones, growth factors, and cytokines on the expression of mRNAs for surfactant proteins A, B, and C (SP-A, SP-B, and SP-C). Our results show that keratinocyte growth factor (KGF) induced a two- to threefold increase in steady-state levels of mRNAs for SP-A and SP-B, but had no effect on or decreased SP-C mRNA. The increase in SP-A mRNA was accompanied by an increase in SP-A protein. The effects of KGF were both dose and time dependent, and they could be neutralized by a monoclonal antibody against KGF. The effects of KGF were mimicked by acidic fibroblast growth factor, which will bind the KGF receptor. We conclude that KGF can support differentiation of alveolar type II cells as well as act as a mitogen, thus suggesting an important role for KGF in maintenance of the alveolar epithelium.
肺表面活性物质是一种由磷脂和肺特异性表面活性蛋白组成的复合物，其产生是肺泡II型细胞的主要功能。尽管先前的研究已经证明细胞-细胞外基质相互作用和正常细胞形态在成年大鼠II型细胞原代培养中维持分化功能方面发挥作用，但尚未有关于生长因子在分离的正常成年II型细胞表面活性蛋白基因表达中起积极作用的报道。在本研究中，我们检测了一组激素、生长因子和细胞因子对表面活性蛋白A、B和C（SP-A、SP-B和SP-C）mRNA表达的影响。我们的结果表明，角质形成细胞生长因子（KGF）使SP-A和SP-B的mRNA稳态水平增加了两到三倍，但对SP-C mRNA没有影响或使其降低。SP-A mRNA的增加伴随着SP-A蛋白的增加。KGF的作用具有剂量和时间依赖性，并且可以被抗KGF单克隆抗体中和。酸性成纤维细胞生长因子可模拟KGF的作用，它能与KGF受体结合。我们得出结论，KGF既能支持肺泡II型细胞的分化，又能作为有丝分裂原，因此表明KGF在维持肺泡上皮中起重要作用。
