These authors contributed equally to this work.
Up-regulation of stomatin expression by hypoxia and glucocorticoid stabilizes membrane-associated actin in alveolar epithelial cells
Version of Record online: 15 MAY 2013
© 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 17, Issue 7, pages 863–872, July 2013
How to Cite
Chen, J.-C., Cai, H.-Y., Wang, Y., Ma, Y.-Y., Song, L.-N., Yin, L.-J., Cao, D.-M., Diao, F., Li, Y.-D. and Lu, J. (2013), Up-regulation of stomatin expression by hypoxia and glucocorticoid stabilizes membrane-associated actin in alveolar epithelial cells. Journal of Cellular and Molecular Medicine, 17: 863–872. doi: 10.1111/jcmm.12069
- Issue online: 24 JUL 2013
- Version of Record online: 15 MAY 2013
- Manuscript Accepted: 24 MAR 2013
- Manuscript Received: 4 APR 2012
- National Natural Science Foundation of China. Grant Number: 91029722
- The National Basic Research Program “973”. Grant Number: 2006CB504100
- actin cytoskeleton;
- alveolar epithelial cells;
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.