Up‐regulation of stomatin expression by hypoxia and glucocorticoid stabilizes membrane‐associated actin in alveolar epithelial cells

Journal of Cellular and Molecular Medicine

Ji-Cheng Chen²  Hao-Yu Cai²  Yan Wang²  Yuan-Yuan Ma²  Liang-Nian Song¹  Li-Juan Yin²  Dong-Mei Cao²  Fei Diao²  Yi-Dong Li² 

[1]Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA

[2]Department of Pathophysiology, The Second Military Medical University, Shanghai, China

关键词: actin cytoskeleton;    alveolar epithelial cells;    dexamethasone;    hypoxia;    stomatin;   

DOI  :  10.1111/jcmm.12069

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

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