Alveolar Epithelial Cell Differentiation and Surfactant Protein Expression After Mild Preterm Birth in Sheep

Abstract

ABSTRACT:As the transition to extrauterine life at birth alters the proportions of type I and II alveolar epithelial cells (AECs), our aim was to determine the effect of mild preterm birth on AECs and surfactant protein (SP) gene expression. Preterm lambs were born at ϳ133 d of gestational age (DGA); controls were born at term (ϳ147 DGA). Lungs were collected from preterm lambs at termequivalent age (TEA; ϳ2 wk after preterm birth) and 6 wk post-TEA. Control lung tissue was collected from fetuses (at 132 DGA), as well as from lambs at ϳ6 h (normal term) and 2, 6, and 8 wk of postnatal age (PNA). In controls, the proportion of type I AECs decreased from 65.1 Ϯ 3.9% at term to 50.9 Ϯ 3.3%, while the proportion of type II AECs increased from 33.7 Ϯ 3.9% to 48.5 Ϯ 3.3% at 6 wk PNA. At 2 wk after preterm birth, the proportions of type I and II AECs were similar in preterm lambs compared to 132-d fetal levels and term controls but differed from control values at 2 wk PNA; differences between control and preterm lambs persisted at 8 wk PNA. At ϳ2 wk after preterm birth, SP-A and SP-B, but not SP-C, mRNA levels were significantly reduced in preterm lambs compared with term controls, but these differences did not persist at 2 and 6 wk PNA. We conclude that mild preterm birth alters the normal postnatal changes in type I and II cell proportions but does not severely affect SP gene expression.

Establishment and Evaluation of a Stable Cattle Type II Alveolar Epithelial Cell Line

“…In the fetus, increased lung expansion promotes differentiation into the type I AEC phenotype, whereas reduced lung expansion promotes the type II AEC phenotype [31,32]. Lung expansions become progressively larger with lung development and excess AEC I may influence AEC II cell purity.…”

Reduced expression of aquaporin 5 water channel in nitrofen-induced hypoplastic lung with congenital diaphragmatic hernia rat model

“…In the fetus, it has been reported that increased expansion promotes differentiation into the AEC-I phenotype, whereas reduced lung expansion promotes the type II alveolar epithelial cells (AECs-II) phenotype [16]. Type II AECs are thought to be progenitor for AECs-I, and the differentiation from AECs-II to AECs-I is one of the most important event in lung development during late gestation [8,16,17]. Some reports have pointed out that the hypoplastic lungs associated with CDH have thick-walled terminal air spaces, no true alveoli, increased frequency of AECs-II, and decreased expression of AECs-I associated protein, RTI 40 [15].…”

Establishment of a highly metastatic model with a newly isolated lung adenocarcinoma cell line

“…Immunofluorescence was performed to detect the expression of pan-cytokeratin (21)(22)(23) to identify the epithelial origin of XL-2. Because surfactant protein C (SP-C) is considered a marker of mature type II alveolar epithelial cells (AEC-II) (24)(25)(26)(27), immunofluorescence was also used to evaluate its expression level. Cells were cultured on glass coverslips for 18-20 h, fixed with 4% paraformaldehyde for 30 min, and permeabilized in 0.25% Triton X-100 for 15 min.…”