Cazals V, Mouhieddine B, Maitre B, Le Bouc Y, Chadelat K, Brody J S, Clement A
Physiology Department, Hospital Trousseau, St. Antoine Medical School, University of Paris.
J Biol Chem. 1994 May 13;269(19):14111-7.
The epithelium of the pulmonary alveolus is a major target for oxidant injury, and its proper repair following injury is dependent on the proliferative response of its stem cells, the type 2 cells. We have recently shown that hyperoxia arrests proliferation of an immortalized type 2 cell line (SV40T-T2) and that expression of several growth-related genes, normally induced near the G1/S and boundary was altered with a block of translation of their mRNA. In the present study we examined the possible role of the insulin-like growth factor (IGF) system and of transforming growth factor-beta 1 (TGF-beta 1) in the arrest of proliferation induced by hyperoxia. We show that IGF-binding protein 2 (IGFBP-2) accumulates to higher levels in culture medium of SV40T-T2 cells whose proliferation has been arrested by hyperoxia. This proliferation arrest is associated with increased expression of IGFBP-2 mRNA and with induction of type 2 IGF receptor and IGF-II mRNAs. When O2-arrested cells were allowed to resume proliferation in normoxia, the level of expression of these genes rapidly decreased to control levels. We also, found that TGF-beta 1 was induced by O2 exposure, that TGF-beta 1 inhibited SV40T-T2 proliferation, and that TGF-beta 1 itself was a potent stimulator of IGFBP-2 expression. These studies suggest a regulatory link between components of the IGF system and TGF-beta 1 in hyperoxic control of cell proliferation of alveolar epithelial cells.
肺泡上皮是氧化损伤的主要靶点，损伤后其正常修复依赖于其干细胞（2型细胞）的增殖反应。我们最近发现，高氧可阻止永生化2型细胞系（SV40T-T2）的增殖，并且一些通常在G1/S期及交界处被诱导表达的与生长相关的基因，其mRNA的翻译受阻，导致表达改变。在本研究中，我们探讨了胰岛素样生长因子（IGF）系统和转化生长因子-β1（TGF-β1）在高氧诱导的增殖阻滞中的可能作用。我们发现，在因高氧而增殖受阻的SV40T-T2细胞的培养基中，IGF结合蛋白2（IGFBP-2）积累到更高水平。这种增殖阻滞与IGFBP-2 mRNA表达增加以及2型IGF受体和IGF-II mRNA的诱导有关。当在常氧条件下让被氧气阻滞的细胞恢复增殖时，这些基因的表达水平迅速降至对照水平。我们还发现，TGF-β1可由氧气暴露诱导产生，TGF-β1可抑制SV40T-T2细胞增殖，并且TGF-β1本身是IGFBP-2表达的有效刺激因子。这些研究表明，在高氧对肺泡上皮细胞增殖的调控中，IGF系统和TGF-β1的各组分之间存在调节联系。
