Regulation of phenotype and gene expression in alveolar epithelial cells

肺泡上皮细胞表型和基因表达的调节

• 批准号: 12670201
• 负责人: SUZUKI Yasuhiro
• 金额: $ 2.11万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670201/
• 关键词: type II cell; transdifferentiation; sulfotransferase; proteoglycan; cell spreading; lung damage; MT-MMP; 肺傷害; 肺胞上皮細胞; 遺伝子発現; ヘパラン硫酸; ハービマイシンA; リチウム

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.

我们在体内外研究了N-脱乙酰酶/磺基转移酶(NDST)在大鼠II型上皮细胞中的表达。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T1a的I型细胞时，可诱导其表达，并与细胞扩散有关。抗NDST抗体在孕16天胎鼠肺上皮细胞中仅有微弱反应，而在成年鼠肺中除Clara细胞和II型细胞外，以后各日龄均未见反应。在盐酸诱导的肺损伤中，病变周围的非典型上皮细胞和病变内的非典型上皮细胞对抗增殖细胞核抗原抗体有反应，提示在治疗第2天有增殖。这些细胞高表达MT2-和1-MMP2。在第7天和第14天，许多II型细胞仍侵袭到纤维化病变中。NDST在第2天开始在这些上皮细胞中显著表达，并在新形成的肺泡中的部分细胞中表达，直到第14天。体外分析表明，去甲氧核霉素A诱导了NDST mRNA的表达，这种诱导作用被蛋白酶体抑制剂所阻断。氯化锂同时抑制NDST的表达和细胞的扩散。氯酸钠也抑制了细胞的扩散。在铺展的细胞中，b-catenin的mRNA和复合体增加，b-catenin定位于肌动蛋白边缘带和外侧。这些结果表明，NDST更多地参与肺损伤的修复，而不是胎肺的形态发生。这些结果表明，NDST在II型细胞迁移、增殖和渗入病变形成新的肺泡后扩散和转分化为I型细胞时表达，b-catenin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，并且是由氯化锂诱导的。

项目成果

Zhong-Yuan Li: "Expression of N-deacetylase/sulfotransferase and 3-O-sulfotransferase in rat alveolar type II cells."Am.J,Physiol.Lung Cell.Mot.Physiol.. 279・2. L292-L301 (2000)

李中元：“大鼠肺泡 II 型细胞中 N-脱乙酰酶/磺基转移酶和 3-O-磺基转移酶的表达”。Am.J,Physiol.Lung Cell.Mot.Physiol.. 279・2. ）

李 中原: "ラット肺胞II型上皮細胞のN-deacetylase/sulfotransferaseの発現に対するherbimycin AとLichium chlorideの影響"日本界面医学会雑誌. 32. 38-45 (2001)

Chunghara Lee：“除草霉素 A 和氯化锂对大鼠肺泡 II 型上皮细胞 N-脱乙酰酶/磺基转移酶表达的影响”日本界面医学会杂志 32. 38-45 (2001)。

Li, Z-Y: "Effect of herbimycin A and lithium chloride on the expression of N-deacetylase sulfo-transferase in rat alveolar type II cells (in Japanese)."J. Japan Med. Soc. Biol. Interface. 32. 38-45 (2001)

Li，Z-Y：“除草霉素 A 和氯化锂对大鼠 II 型肺泡细胞 N-脱乙酰酶磺基转移酶表达的影响（日语）”。

李 中原: "ラット肺胞II型上皮細胞のN-deacetylace/sulfotransferaseの発現に対するherbimyciuAとlithium chlorideの影響"日本界面医学会雑誌. 32. 38-45 (2001)

zhonghara Lee：“herbimyciuA和氯化锂对大鼠肺泡II型上皮细胞中N-脱乙酰基/磺基转移酶表达的影响”日本界面医学会杂志32. 38-45（2001）。

Zhong-Yuan Li: "Expression of N-deacetylase/sulfotransferase and 3-O-sulfotransferase in rat alveolar type II cells"Am. J. Physiol. Lung Cell. Physiol.. 279. L292-L301 (2000)

李中元：“大鼠肺泡II型细胞中N-脱乙酰酶/磺基转移酶和3-O-磺基转移酶的表达”Am。