title: Up-regulation of stomatin expression by hypoxia and glucocorticoid stabilizes membrane-associated actin in alveolar epithelial cells.
abstract: Stomatin is an important lipid raft-associated protein which interacts with membrane proteins and plays a role in the membrane organization. However, it is unknown whether it is involved in the response to hypoxia and glucocorticoid (GC) in alveolar epithelial cells (AEC). In this study we found that hypoxia and dexamethasone (dex), a synthetic GC not only up-regulated the expression of stomatin alone, but also imposed additive effect on the expression of stomatin in A549 cells, primary AEC and lung of rats. Then we investigated whether hypoxia and dex transcriptionally up-regulated the expression of stomatin by reporter gene assay, and found that dex, but not hypoxia could increase the activity of a stomatin promoter-driven reporter gene. Further deletion and mutational studies demonstrated that a GC response element (GRE) within the promoter region mainly contributed to the induction of stomatin by dex. Moreover, we found that hypoxia exposure did not affect membrane-associated actin, but decreased actin in cytoplasm in A549 cells. Inhibiting stomatin expression by stomatin siRNA significantly decreased dense of peripheral actin ring in hypoxia or dex treated A549 cells. Taken all together, these data indicated that dex and/or hypoxia significantly up-regulated the expression of stomatin in vivo and in vitro, which could stabilize membrane-associated actin in AEC. We suppose that the up-regulation of stomatin by hypoxia and dex may enhance the barrier function of alveolar epithelia and mediate the adaptive role of GC to hypoxia.
authors.affiliation: Department of Pathophysiology, The Second Military Medical University, Shanghai, China.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Chen
authors.forename: Hao-Yu
authors.initials: HY
authors.lastname: Cai
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ma
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Song
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Yin
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Cao
authors.forename: Fei
authors.initials: F
authors.lastname: Diao
authors.forename: Yi-Dong
authors.initials: YD
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D000199:Actins; D008565:Membrane Proteins; C036860:STOM protein, human; C555926:Stom protein, rat; D003907:Dexamethasone
keywords: actin cytoskeleton; alveolar epithelial cells; dexamethasone; hypoxia; stomatin