Published ahead of print on June 16, 2005, doi:10.1165/rcmb.2005-0144OC Am. J. Respir. Cell Mol. Biol., Volume 33, Number 3, September 2005, 297-302 A more recent version of this article appeared on September 1, 2005
Submitted on April 18, 2005 Cyr61 Protects Against Hyperoxia Induced Cell Death via Akt Pathway in Pulmonary Epithelial CellsYang Jin1,1 Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA, 2 Department of Biochemistry and Molecular Genetics, University of Illnois at Chicago, Chicago, IL, USA * To whom correspondence should be addressed. E-mail: ChoiAM{at}MSX.UPMC.EDU.
We have used gene expression profiling approaches to identify new molecular targets in various models of lung injury and human lung diseases. Among the many genes which are significantly induced in these studies, cysteine-rich61 (Cyr61) consistently ranks one of the most significant genes. Here, we use the well-established model of hyperoxia to better understand the function of Cyr61 in acute lung injury. Cyr61, a stress related immediate-early response gene, has known diverse functions involving angiogenesis, tumorigenesis and wound repair. It belongs to the newly discovered "CCN" family containing six growth and regulatory factors. We showed that hyperoxia induces Cyr61 expression in a variety of pulmonary cells and in lung tissue in vivo. Loss of function studies by suppressing Cyr61 expression by siRNA accelerated lung epithelial cell death after hyperoxia. Gain of function studies by over-expressing Cyr61 significantly conferred increased resistance to hyperoxia induced cell death. Moreover, cells overexpressing Cyr61 induces Akt activation. Inhibition of Akt by siRNA abrogated the protective effects of Cyr61 over-expressing cell in response to hyperoxia. Taken together, our data demonstrate that Cyr61 expression provides cytoprotection in hyperoxia induced pulmonary epithelial cell death and this effect was in part mediated via the Akt signaling pathway.
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
