Cyr61 protects against hyperoxia-induced cell death via Akt pathway in pulmonary epithelial cells

Yang Jin, Hong Pyo Kim, Emeka Ifedigbo, Lester F. Lau, Augustine M K Choi

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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 that are significantly induced in these studies, cysteine-rich61 (Cyr61) consistently ranks as 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 overexpressing Cyr61, significantly conferred increased resistance to hyperoxia-induced cell death. Moreover, cells overexpressing Cyr61 induce Akt activation. Inhibition of Akt by siRNA abrogated the protective effects of Cyr61-overexpressing cells in response to hyperoxia. Taken together, our data demonstrate that Cyr61 expression provides cytoprotection in hyperoxia-induced pulmonary epithelial cell death and that this effect was in part mediated via the Akt signaling pathway.

Original languageEnglish (US)
Pages (from-to)297-302
Number of pages6
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume33
Issue number3
DOIs
StatePublished - Sep 1 2005

Keywords

  • Akt
  • Cell death
  • Cyr61
  • Hyperoxia
  • Lung

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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