Insulin-like growth factors, their binding proteins, and transforming growth factor-beta 1 in oxidant-arrested lung alveolar epithelial cells.
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.
Cazals
V
V
Physiology Department, Hospital Trousseau, St. Antoine Medical School, University of Paris.
Mouhieddine
B
B
Maitre
B
B
Le Bouc
Y
Y
Chadelat
K
K
Brody
J S
JS
Clement
A
A
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2; D008969:Molecular Sequence Data; D016877:Oxidants / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism*
D002352:Carrier Proteins; D017931:DNA Primers; D018971:Insulin-Like Growth Factor Binding Protein 2; D016877:Oxidants; D012333:RNA, Messenger; D013002:Somatomedins; D016212:Transforming Growth Factor beta; D010100:Oxygen