Mechanical distension modulates pulmonary alveolar epithelial phenotypic expression in vitro

Mechanical distension modulates pulmonary alveolar epithelial phenotypic expression in vitro
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DOI:
10.1152/ajplung.1998.274.2.l196
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发表时间:
1998-02-01
影响因子:
4.9
通讯作者:
Dobbs, LG
Dobbs, LG
中科院分区:
医学2区
文献类型:
--
作者:
Gutierrez, JA;Gonzalez, RF;Dobbs, LG

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肺泡上皮由两种不同类型的细胞组成,I型和II型细胞,这两种细胞对正常的肺功能都至关重要。在自然和体内实验的基础上,人们假设I型或II型表型的表达受到机械因素的影响。我们研究了机械膨胀对培养的肺泡II型细胞中I型和II型细胞表型特异性标志物表达的影响。大鼠肺泡II型细胞在培养中呈强直性机械膨胀。对细胞进行I型表型标记物(rTI(40),一种I型细胞特有的完整膜蛋白)和II型表型标记物[表面活性剂蛋白(SP) a、SP- b和SP- c]以及甘油醛-3-磷酸脱氢酶(GAPDH)的分析。与未膨胀对照组相比,机械膨胀导致rTI(40) mRNA含量增加68 +/- 25% (n = 3)。相比之下,机械膨胀导致未膨胀对照组SP-B mRNA含量下降至35 +/- 19% (n = 3), SP-C mRNA含量下降至20 +/- 6.7% (n = 3)。对mRNA无影响。SP-A或GAPDH的含量。通过细胞核运行试验发现SP-B和SP-C mRNA含量的差异主要是由于转录水平的变化。对rTI(40)的影响似乎是由于转录后事件。这些数据表明,机械膨胀影响肺泡上皮在体外的表型表达,至少部分,在转录水平。
The pulmonary alveolar epithelium is composed of two distinct types of cells, type I and type II cells, both of which are critical for normal lung function. On the basis of experiments of both nature and in vivo studies, it has been hypothesized that expression of the type I or type II phenotype is influenced by mechanical factors. We have investigated the effects of mechanical distension on the expression of specific markers for the type I and type II cell phenotypes in cultured alveolar type II cells. Rat alveolar type II cells were tonically mechanically distended in culture. Cells were analyzed for a marker for the type I phenotype (rTI(40), an integral membrane protein specific for type I cells) and for markers for the type II phenotype [surfactant protein (SP) A, SP-B, and SP-C] as well as for glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Mechanical distension caused a 68 +/- 25% (n = 3) increase in mRNA content of rTI(40) relative to undistended controls. In contrast, mechanical distension resulted in a decrease in mRNA content of SP-B to 35 +/- 19% (n = 3) and of SP-C to 20 +/- 6.7% (n = 3) of undistended controls. There was no effect on mRNA. content of SP-A or GAPDH. The differences in mRNA content of SP-B and SP-C were found to be primarily due to changes at the transcriptional level by nuclear run-on assays. The effects on rTI(40) appear to be due to posttranscriptional events. These data show that mechanical distension influences alveolar epithelial phenotypic expression in vitro, at least in part, at the transcriptional level.