Gutierrez J A, Ertsey R, Scavo L M, Collins E, Dobbs L G
Departments of Pediatrics and Medicine and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA.
Am J Respir Cell Mol Biol. 1999 Aug;21(2):223-9. doi: 10.1165/ajrcmb.21.2.3665.
The development of a normal pulmonary alveolar epithelium, essential for gas exchange, is critical for the successful adaptation to extrauterine life. From observations of natural and experimental developmental abnormalities, it has been hypothesized that mechanical factors may play a role in regulating differentiation of the pulmonary alveolar epithelium. To test this hypothesis directly, we have investigated the in vitro effects of mechanical distention on the expression of specific markers for the type I and type II cell phenotypes. Fetal rat lung (18-d) explants were mechanically distended in culture for 18 h. Mechanical distention caused an increase in RTI 40 messenger RNA (mRNA), a marker of the type I cell phenotype, of 10.6 times (n = 3, P < 0.05) that of undistended controls. In contrast, mechanical distention resulted in a decrease in mRNA content of two markers of the type II cell phenotype, surfactant protein (SP)-B and SP-C. SP-B was reduced to 10 +/- 9% (n = 3, P < 0.005) and of SP-C to 12 +/- 7% (n = 3, P < 0.0001) of undistended controls. Mechanical distention had no effect on content of mRNA for SP-A or 18S ribosomal RNA. Examined by nuclear run-on assays, mechanical distention caused changes in transcriptional rates of RTI 40, SP-B, and SP-C. These data show that mechanical distention stimulates expression of a type I cell marker and inhibits expression of markers for the type II phenotype; these effects occur at least in part at the transcriptional level. These studies support the hypothesis that mechanical distention of fetal lung tissue stimulates expression of the type I cell phenotype and inhibits expression of the type II phenotype.
正常肺泡上皮的发育对于气体交换至关重要，是成功适应宫外生活的关键。通过对自然和实验性发育异常的观察，有人推测机械因素可能在调节肺泡上皮细胞分化中起作用。为了直接验证这一假设，我们研究了机械扩张对I型和II型细胞表型特异性标志物表达的体外影响。将18天龄胎鼠肺组织外植体在培养中进行机械扩张18小时。机械扩张使I型细胞表型标志物RTI 40信使核糖核酸（mRNA）增加，是未扩张对照组的10.6倍（n = 3，P < 0.05）。相反，机械扩张导致II型细胞表型的两个标志物表面活性蛋白（SP）-B和SP-C的mRNA含量降低。SP-B降至未扩张对照组的10±9%（n = 3，P < 0.005），SP-C降至12±7%（n = 3，P < 0.0001）。机械扩张对SP-A或18S核糖体RNA的mRNA含量没有影响。通过核转录分析检测，机械扩张导致RTI 40、SP-B和SP-C的转录速率发生变化。这些数据表明，机械扩张刺激I型细胞标志物的表达并抑制II型表型标志物的表达；这些效应至少部分发生在转录水平。这些研究支持了胎儿肺组织的机械扩张刺激I型细胞表型表达并抑制II型表型表达的假设。
