Regulation of phenotype and gene expression in alveolar epithelial cells

我们研究了N-脱乙酰基酶/磺基转移酶（NDST）在大鼠II型上皮细胞在体外和体内的表达。NDST mRNA的表达依赖于细胞密度和基质。当II型上皮细胞转分化为表达T1 a的I型细胞时，它被诱导，并与细胞扩散相关。抗NDST抗体仅与孕16天的胎鼠肺上皮细胞有轻微反应，而在以后各年龄段的肺中除Clara细胞和Ⅱ型细胞外均无反应。在盐酸诱导的肺损伤，病变周围的非典型上皮细胞和浸润到病变的抗PCNA抗体反应，表明在治疗第2天增殖。这些细胞高表达MT 2-和1-MMP。在第7天和第14天，许多II型细胞仍然侵入纤维化病变。NDST在第2天在这些上皮细胞中显着表达，并且在新形成的肺泡中的一些细胞中直到第14天。体外分析表明，除莠霉素A诱导NDST mRNA的表达，这种诱导被蛋白酶体抑制剂废除。氯化锂抑制NDST表达和细胞铺展。氯酸钠也抑制细胞铺展。在伸展细胞中，mRNA和复合形式的b-连环蛋白增加，b-连环蛋白定位于肌动蛋白边缘带和其外部。这些结果表明，NDST参与肺损伤的修复而不是胎儿肺形态发生，并且在II型细胞迁移后伸展和转分化为I型细胞时表达，增殖和浸润到病变中以形成新的肺泡，并且b-连环蛋白是NDST表达的调节因子之一，因为NDST表达的抑制因子对蛋白酶体敏感并且由氯化锂诱导。

We investigated the expression of N-deacetylase/sulfotransferase (NDST) in rat type II epithelial cells in vitro and in vivo. Expression of NDST mRNA depended on cell density and matrix. It was induced when type II epithelial cells transdifferentiated to T1a-expressing type I cells and correlated with cell spreading. Anti-NDST antibody only slightly reacted to the epithelial cells in lungs from fetal rats at 16th day of pregnancy but no reaction was obtained in the lungs at later ages except Clara cells and type II cells in adult rats. In HCl-induced lung damage, atypical epithelial cells surrounding the lesion and those infiltrating into the lesion reacted to anti-PCNA antibody suggesting proliferating at day 2 of treatment. These cells highly expressed MT2- and 1-MMP. At days 7 and 14, many type II cells still invaded into the fibrotic lesion. NDST was remarkably expressed in these epithelial cells at day 2 and was in some cells in the newly formed alveoli until day 14. In vitro analysis revealed that herbimycin A induced expression of NDST mRNA and this induction was abolished by proteasome inhibitors. Lithium chloride inhibited both NDST expression and cell spreading. Sodium chlorate also inhibited cell spreading. In spreading cells, mRNA and complexed form of b-catenin increased and b-catenin was localized at the actin marginal band and outside of it.These results suggest that NDST is involved rather in the repair of lung damage than in fetal lung morphogenesis and is expressed when type II cells spread and transdifferentiate into type I cells after migration, proliferation and infiltration into the lesion to form new alveoli and that b-catenin is one of the regulators of NDST expression, since the inhibitory factor for NDST expression is sensitive to proteasome and is induced by lithium chloride.